Premium Sensor PLUS Man Dr. John Smith DEMO5
COVER LETTER
Dear Mr. Dr. Muster Mustermann, Your sample for the analysis arrived on 01/06/2014 in the laboratory and was evaluated according to the highest laboratory quality standards (ISO 15189 and ISO 17025). The results were evaluated by two independent geneticists and molecular biologists and personally approved by me, the laboratory manager. After obtaining the results, your personal report was compiled. I would like to send this to you in the format of your choice. I would like to thank you for your trust and I hope that you are satisfied with our service. If you have any problems or complaints, please do not hesitate to contact us. This is the only way we can continuously improve our services. I hope the analysis meets your expectations. Kind regards,
Dr. Daniel Wallerstorfer, B.Sc. Laboratory director
Premium Sensor PLUS Male
Personal analysis results for:
Dr. Muster Mustermann | Date of birth: 01/01/1985 Order number:
DEMO_DNAMEDIC
This report contains personal genetic data and is to be treated confidentially.
Table of contents Grayed-out sections are optional elements that were not ordered and are not included in the brochure. GENERAL INFORMATION How genes influence our health
1
PHARMACO GENETICS Pharmaco Sensor (Drug side effects)
5
HIV Sensor (HIV resistance)
27
ONCOLOGY Breast Health Sensor (Breast Cancer)
$*$
ANDROLOGY Prostate Health Sensor (Prostate Cancer)
33
CARDIOVASCULAR SYSTEM Cardiovascular sensor (cardiovascular disease)
45
Thrombo Sensor (Thrombosis)
62
Hypertension Sensor (Hypertonia)
70
METABOLISM Toxo Sensor (Detoxification of toxins)
77
Diabetes Sensor (Diabetes Type 2)
91
Alzheimer Sensor (Alzheimer's Disease)
102
Iron Sensor (Hemochromatosis)
110
MOBILITY Bone Health Sensor (Osteoporosis)
115
Joint Sensor (Rheumatoid Arthritis)
124
DIGESTION Gluten Sensor (Celiac Disease)
131
Lactose Sensor (Lactose Intolerance)
136
IBD Sensor (Inflammatory Bowel Disease)
141
OPHTHALMOLOGY Glaucoma Sensor (Glaucoma)
147
AMD Sensor (Macular Degeneration)
152
ODONTOLOGY Periodontitis Sensor (Periodontitis)
158
GENERAL INFORMATION Technical details
169
References
170
GENETICS
How genes influence our health The human body consists of about 50 trillion individual cells. Most of these cells have a nucleus which contains 46 chromosomes. A chromosome consists of a very closely wound thread, the DNA "double helix." Chromosome
Cells Body (50 trillion cells)
DNA double helix
Lactose gene (LCT)
A = healthy G = risk
DNA, the genetic code, is the blueprint of the human body. This genetic code consists of approximately 3.1 billion molecules, which are each represented by a letter. About 1% of this code makes up the genes. Each gene is an instruction for the body, usually with a single function. For example, some genes tell the body how to generate the iris. Differences in these genes produce different eye colors. Every function of the body is controlled by one or more genes, including the way we process food and medicine.
Thrombosis gene (FV)
Our genes are not completely error-free. The genes of each person are changed slightly by environmental effects. Most of these changes have no effect. A small number have a harmful effect. An even tinier number can produce a beneficial effect. Parents pass these changes, including defects, to their children. Thus most of our genetic defects are inherited from our parents. In addition, our genes developed to help us live in the primitive world, and some of the traits in our genes can interact with our modern environment to create negative effects on our world. For example, the genetic predisposition to build up fat quickly and lose it slowly is beneficial for people who go through times when food is scarce: they will have a better chance of
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surviving because their bodies use fat efficiently. However, in the modern world, this trait is harmful because it programs the body to gain weight quickly and lose weight slowly. Genes increase our risk of heart attacks, trigger asthma and allergies, cause lactose intolerance, and many other disorders. Genetic traits can affect our health. While some genetic defects always cause disease, most genetic traits just increase our risk of getting a disease. For example, a person may have genes that increase their risk for diabetes. However, not everyone at risk for diabetes actually develops the disease. Furthermore, even people with a high risk of diabetes can lower their risk with the right diet and exercise plan. Other genetic traits only cause illness when they are triggered by a specific environmental feature. For example, lactose intolerance is a genetic condition that causes a person who drinks milk to become ill. However, a lactose-intolerant person who never drinks milk will not have any symptoms. Thanks to the latest technologies, it is now possible to test specific genes to determine if you have genetic traits that are linked to various diseases. Based on the results of the analysis, we can develop a prevention program that significantly reduces your personal disease risk and helps you stay healthy. A healthy lifestyle will decrease your risk of many diseases whether or not you have specific information about your genetic traits. However, DNA Plus provides you with additional information that may point out other changes to your lifestyle that are not part of standard medical advice. There are many examples, but one of the traits we test for is a gene that impairs your body’s ability to absorb iron. If you have this trait, we will recommend that you take iron supplements beyond the general recommendations so that your body absorbs all the iron you need. Experts estimate that every person carries about 2,000 genetic defects, which may affect their health, and, in some cases, cause illnesses. A variety of factors can cause changes in our genes (also called mutations). In a few cases, these mutations can benefit us. However, the vast majority either have no effect or have a negative impact on our health. The best-known cause of mutations, as depicted in the media and Hollywood, is radioactivity. Radioactive rays and particles actually impact the DNA in our cells and physically alter our genes. In the movies, these changes or mutations often lead to the creation of monsters like Godzilla, or characters with supernatural powers, as in X-Men. In reality, they mostly go unnoticed or cause deadly diseases, such as cancer, or congenital abnormality for newborns. Mutations are also caused by substances such as carbon, which can be ingested from burnt food. Carbon enters the cells and damages our genes, which can lead to colon cancer, among other form of cancer. UV radiation from the sun can also damage our genes and cause diseases such as skin cancer. External influences can affect individual genes and disrupt their function, but the majority of our defective genes are inherited from our parents. Each embryo receives half of its genes from the father and half of its genes from the mother, resulting in a new human being with some of the characteristics of each parent. The genetic defects are unfortunately passed together with these genes; for example, a genetic defect that causes heart attack may pass from the father to the child and further to the grandchild and so on, leading to passing the same disease to each generation. Whether the genetic defect is passed, however, is determined randomly, and it may be that some of the grandchildren carry the defective gene and others do not.
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Each person is the unique product of generations of accumulation and combination of different genetic traits. Some of those traits have negative effects on our health. With the latest technology, it is now finally possible to examine one's genes and determine his personal health risks and strengths. In many cases, taking advantage of this knowledge, and following some precautionary measures, the diseases may even be prevented. This is the next step in preventive medicine and a new generation of health care.
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Action index Areas highlighted in red should be discussed with your doctor. There is no generally increased risk for the other areas, and thus no special action is required.
Pharmaco Sensor
Take Action ▲
HIV Sensor
Take Action ▲
Prostate Health Sensor
normal ▲
Cardiovascular Sensor
Take Action ▲
Thrombo Sensor
normal ▲
Hypertonia Sensor
normal ▲
Toxo Sensor
Take Action ▲
Diabetes Sensor
Take Action ▲
Alzheimer Sensor
normal ▲
Iron Sensor
Take Action ▲
Bone Health Sensor
normal ▲
Joint Sensor
normal ▲
Gluten Sensor
normal ▲
Lactose Sensor
normal ▲
IBD Sensor
Take Action ▲
Glaucoma Sensor
normal ▲
AMD Sensor
normal ▲
Periodontitis Sensor
Take Action ▲
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Prevention Early diagnosis Treatment
PHARMACO SENSOR Avoiding side effects from medication and improving the outcome • Analysis of 22 genetic variations in eight genes • Potential effects and side effects estimation of over 244 common medications • Degradation, activation and conversion rate of each drug • Medications for over 30 areas of specialty • Avoid side effects • Increase the success of the therapy
PHARMACO GENETICS
How drugs operate in our body Each person reacts differently to drugs. Some people benefit significant from a particular medication, while others experience side effects with symptoms that can range from mild to fatal. According to estimates, approximately 7% of patients suffer from severe adverse reactions and about 0.4% suffer fatal consequences. Adverse reactions to drugs are the fifth most frequent cause of death in the Western world. In most cases, these reactions are determined by inherited genetic variations or interactions between certain drugs.
The path of drugs through our body
drug is taken Drug shows effect
enzyme gene
drug is prepared for breakdown by enzyme
If a drug is taken or injected with a needle, it first enters the bloodstream, through which it reaches the target organ. The drug is recognised by certain enzymes which break it down and remove it from the bloodstream. This causes most drugs to lose their effect. The deactivated drug is then filtered out of the blood with the help of the kidney and finally excreted with urine.
drug enters urine
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Long-term Drug Treatment Due to the fact that many drugs operate over a long period of time, they need to be taken in regular intervals to ensure that the amount of the drug in the bloodstream is kept in the correct range.
administration
Drug in blood active range of drug
0h
8h
16h
24h
32h
Time (hours) This is how the drug always remains at the right concentration and shows its intended effect.
Genetic defects inhibit the break down of the drug Unfortunately, many people carry a defect in one of the enzyme-producing genes that are crucial in this process.
drug is taken
Drug shows effect
enzyme gene
drug is not filtered out of bloodstream
The drug still enters the blood circulation and has its effect, but enzymes do not break it down and it remains in the body for a significantly longer period of time. This is only a minor problem after only one dose, but when a person takes warfarin three times a day, the level of warfarin in the blood gradually increases until it leads to toxic side effects.
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The problem with regular administration of a drug when there is a genetic defect In the case of blood thinners, drug action is at the right level in the beginning of therapy, but the concentration of the drug rises constantly with every administration until it reaches to the point of causing uncontrolled bleeding.
genetic defect slows breakdown of drug
toxic concentration >>> adverse reactions
administration Drug in blood
active range of drug
0h
8h
16h Time (hours)
24h
32h
This means that the 20% of the population that carry a genetic defect need a significantly lower dose of warfarin because the usual dose could lead to serious adverse reactions.
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Prodrugs, the precursors of active drugs Some drugs, so-called "prodrugs", are taken in an inactive form and are only activated by the enzymes of the body. Examples for this kind of drugs include the cancerprevention drug tamoxifen and the painkiller codeine. A prodrug enters the bloodstream in its inactive form. Enzymes in the blood transform it into its active form, and then it takes effect. For example, the painkiller codeine is transformed into morphine in this way and then relieves pain.
drug is taken
enzyme gene
Drug is activated by enzyme Drug shows effect
drug enters urine
In some people, the enzyme that converts a specific prodrug into a drug does not function, so that the drug never has an effect on the body, other than potential side effects. In the case of codeine, there is no pain relief after taking the drug and an alternative drug needs to be chosen. In case of tamoxifen, a drug that prevents the emergence of breast cancer, the drug's ineffectiveness will only be discovered if cancer develops.
drug is taken Drug shows no effect
enzyme gene
Drug is not activated
drug is not filtered out of bloodstream
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Dosage instructions for the physician This genetic analysis provides information on the rate of absorption of various medications. This information is one factor among many that should be used to determine the optimal dosage of a medication. This data cannot replace your professional opinion and responsibility for proper dosage. With that in mind, the genetic analysis indicates that the following dosages would generally be appropriate for a patient with this genetic profile:
Recommended dosage: ~100% This is the normal state when the relevant genes do not contain any performance-reducing gene variations. Administrate the medication as usual.
Recommended dosage: ~20%, ~50%, ~70% etc. The enzymes involved in the absorption of this medication have limited function and the absorption rate is probably very low. Alternative compounds will most likely be more effective. If absolutely necessary, use this drug with close surveillance for effectiveness and side effects.
Recommended dosage: 0% The enzymes involved in the absorption of this medication have limited function and the absorption rate is probably very low. Alternative compounds will most likely be more effective. If absolutely necessary, use this drug with close surveillance for effectiveness and side effects.
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PHARMACO GENETICS
Pharmacogenetic genes The following genes and polymorphisms have an impact on the breakdown and effect of various drugs. You genetic analysis found the following: Pharmacogenetics Drug Category 1
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 2D6
2549 A/del (Allele*3)
active
rapid
Cytochrome P-450 2D6
1846 G/A (Allele*4)
inactive
slow
Cytochrome P-450 2D6
1707 T/del (Allele*6)
active
rapid
Cytochrome P-450 2D6
2935 A/C (Allele*7)
active
rapid
Cytochrome P-450 2D6
1758 G/T (Allele*8/14)
active
rapid
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
POOR METABOLIZER Your result
Drug Category 2
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 2C9
Arg144Cys (Allele*2)
active
rapid
Cytochrome P-450 2C9
Ile359Leu (Allele*3)
active
rapid
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
POOR METABOLIZER
Your result
Drug Category 3
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 2C19
681 G/A (Allele*2)
active
rapid
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
POOR METABOLIZER
Your result
Drug Category 4
polymorphism
condition of gene
drug metabolism
NAT2
G191A
normal
normal
NAT2
C282T
normal
normal
NAT2
T341C
normal
normal
NAT2
C481T
normal
normal
NAT2
G590A
normal
normal
NAT2
A803G
normal
normal
NAT2
G857A
normal
normal
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
Your result
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POOR METABOLIZER
Drug Category 5
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 3A4
rs28371759 (Allele*18)
active
rapid
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
POOR METABOLIZER
Your result
Drug Category 6
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 3A5
rs776746 (Allele*1)
inactive
slow
ULTRA RAPID METABOLIZER
RAPID METABOLIZER
EXTENSIVE METABOLIZER
POOR METABOLIZER
Your result
Drug Category 7
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 2E1
rs72559710 (Allele*2)
active
rapid
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
POOR METABOLIZER
Your result
Drug Category 8
polymorphism
condition of gene
drug metabolism
Cytochrome P-450 1A2
rs2069514 (*1C)
inhibited
inhibited
Cytochrome P-450 1A2
rs762551 (*1F)
active
very rapid
ULTRA RAPID METABOLIZER
EXTENSIVE METABOLIZER
INTERMEDIATE METABOLIZER
POOR METABOLIZER
Your result
Genetic variations SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
NOS1AP
rs10494366
T>G
T/G
-
RESPOND
-
RISK
VKORC
rs9923231
C>T
C/C
-
-
-
-
LEGEND: ULTRA RAPID METABOLIZER = The enzymes for this group of drugs are too active and convert the medication too fast and remove it from the body. EXTENSIVE METABOLIZER = enzymes are functional and modify and break down certain drugs rapidly. INTERMEDIATE METABOLIZER = enzymes are inhibited or produced at a lower rate leading to a slower and break down of certain drugs. POOR METABOLIZER = no functional enzymes are being produced and so certain drugs are not broken down or metabolized correctly.
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PHARMACO GENETICS
Effect on relevant drugs Drugs for epilepsy (anticonvulsant) Drugs for the treatment of epilepsy
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
diazepam (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
mephenytoin
Normal
~100%
Normal
~100%
Not neccessary
phenobarbital
Normal
~100%
Normal
~100%
Not neccessary
phenytoin
Normal
~100%
Normal
~100%
Not neccessary
primidone
Normal
~100%
Normal
~100%
Not neccessary
retigabine
Normal
~100%
Normal
~100%
Not neccessary
zonisamide
Normal
~100%
Normal
~100%
Not neccessary
Cough surpressants (antitussive) Drugs for suppressing cough
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
dextromethorphan (FDA!)
None/Low
~0%
common
0%
Advisable
Drugs for allergies (antihistaminea) Drugs for the treatment of allergic reactions
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
astemizole
Normal
~100%
Normal
~100%
Not neccessary
chlorphenamine
Normal
~100%
Normal
~100%
Not neccessary
salmeterol
Normal
~100%
Normal
~100%
Not neccessary
terfenadine
likely higher
~100%
Normal
~100%
Not neccessary
theophylline
likely higher
~100%
Normal
~100%
Not neccessary
zileuton
Normal
~100%
Normal
~100%
Not neccessary
Appetite suppressants (anorectic) Hunger suppressants
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
dexfenfluramine
Normal
~0%
common
0%
Advisable
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Immunosuppressive Drugs that suppress the immune system
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
ciclosporin
Normal
~100%
Normal
~100%
Not neccessary
sirolimus
Normal
~100%
Normal
~100%
Not neccessary
tacrolimus
Normal
~100%
Normal
~100%
Not neccessary
Drugs for hyperactivity (stimulants) Drugs for the treatment of hyperactivity or narcolepsy
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amphetamin
Normal
~0%
common
0%
Advisable
amphetamine
Normal
~0%
common
0%
Advisable
atomoxetine (FDA!)
Normal
~0%
common
0%
Advisable
Other drugs
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
carisoprodol (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
cevimeline
Normal
~100%
Normal
~100%
Not neccessary
chlorzoxazone
Normal
~100%
Normal
~100%
Not neccessary
cisapride
Normal
~100%
Normal
~100%
Not neccessary
dexlansoprazole (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
finasteride
Normal
~100%
Normal
~100%
Not neccessary
modafinil (FDA!)
Normal
~0%
common
0%
Advisable
progesterone
Normal
~100%
Normal
~100%
Not neccessary
riluzole
Normal
~100%
Normal
~100%
Not neccessary
sildenafil
Normal
~100%
Normal
~100%
Not neccessary
tadalafil
Normal
~100%
Normal
~100%
Not neccessary
tetrabenazine (FDA!)
Normal
~0%
common
0%
Advisable
tizanidine
Normal
~100%
Normal
~100%
Not neccessary
tolterodine (FDA!)
Normal
~0%
common
0%
Advisable
Other
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Hormones sex hormones
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
bicalutamide
Normal
~100%
Normal
~100%
Not neccessary
estradiol
Normal
~100%
Normal
~100%
Not neccessary
ethinylestradiol
Normal
~100%
Normal
~100%
Not neccessary
testosterone
Normal
~100%
Normal
~100%
Not neccessary
toremifene
Normal
~100%
Normal
~100%
Not neccessary
Drugs for the treatment of stomach ulcers
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
esomeprazole (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
lansoprazole (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
omeprazole (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
pantoprazole (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
rabeprazole (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
Drugs for the treatment of psychoses
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
aripiprazole (FDA!)
Normal
~10%
common
0%
Advisable
chlorpromazine
Normal
~0%
common
0%
Advisable
clobazam (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
clozapine (FDA!)
Normal
~20%
common
~20%
Advisable
escitalopram
Normal
~100%
Normal
~100%
Not neccessary
Proton pump inhibitors
Antipsychotics
haloperidol
Normal
~50%
common
~50%
Advisable
iloperidone (FDA!)
Normal
~0%
common
0%
Advisable
olanzapine
Normal
~50%
common
~50%
Advisable
perphenazine (FDA!)
Normal
~0%
common
0%
Advisable
pimozide (FDA!)
Normal
~20%
common
~20%
Advisable
quetiapine
Normal
~100%
Normal
~100%
Not neccessary
remoxipride
Normal
~0%
common
0%
Advisable
risperidone (FDA!)
Normal
~0%
common
0%
Advisable
thioridazine (FDA!)
Normal
~0%
common
0%
Advisable
ziprasidone
Normal
~100%
Normal
~100%
Not neccessary
zuclopenthixol
Normal
~0%
common
0%
Advisable
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Antidepressants Drugs for the treatment of clinical depression
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
agomelatine
Normal
~100%
Normal
~100%
Not neccessary
amitriptyline
likely higher
~20%
common
~20%
Advisable
buspirone
Normal
~100%
Normal
~100%
Not neccessary
citalopram
Normal
~55%
common
~50%
Advisable
clomipramine
Normal
~50%
common
~50%
Advisable
cyclobenzaprine
Normal
~100%
Normal
~100%
Not neccessary
desipramine
Normal
~20%
common
~20%
Advisable
diazepam
likely higher
~100%
Normal
~100%
Not neccessary
doxepin
Normal
~0%
common
0%
Advisable
duloxetine
Normal
~50%
common
~50%
Advisable
fluoxetine
Normal
~30%
common
~20%
Advisable
fluvoxamine
Normal
~0%
common
0%
Advisable
imipramine
Normal
~50%
common
~50%
Advisable
mianserin
Normal
~0%
common
0%
Advisable
minaprine
Normal
~0%
common
0%
Advisable
mirtazapine
Normal
~55%
common
~50%
Advisable
moclobemide
Normal
~50%
common
~50%
Advisable
nefazodone
Normal
~20%
common
~20%
Advisable
norfluoxetine
Normal
~50%
common
~50%
Advisable
nortriptyline
Normal
~0%
common
0%
Advisable
paroxetine
Normal
~0%
common
0%
Advisable
protriptyline
Normal
~0%
common
0%
Advisable
reboxetine
Normal
~100%
Normal
~100%
Not neccessary
sertraline
Normal
~100%
Normal
~100%
Not neccessary
trazodone
Normal
~50%
common
~50%
Advisable
trimipramine (FDA!)
Normal
~50%
common
~50%
Advisable
valproicacid
Normal
~100%
Normal
~100%
Not neccessary
venlafaxine (FDA!)
likely higher
~18%
common
0%
Advisable
Page 16 of 180
Drugs for Infections (antibiotics etc.) Medication to combat infections
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
caspofungin
Normal
~100%
Normal
~100%
Not neccessary
clarithromycin
Normal
~100%
Normal
~100%
Not neccessary
dapsone
Normal
~100%
Normal
~100%
Not neccessary
erythromycin
Normal
~100%
Normal
~100%
Not neccessary
indinavir
Normal
~100%
Normal
~100%
Not neccessary
isoniazid (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
itraconazole
Normal
~100%
Normal
~100%
Not neccessary
ketoconazole
Normal
~100%
Normal
~100%
Not neccessary
nelfinavir
Normal
~100%
Normal
~100%
Not neccessary
nevirapine
Normal
~100%
Normal
~100%
Not neccessary
proguanil
likely higher
~100%
Normal
~100%
Not neccessary
pyrazinamide (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
rifampin (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
ritonavir
Normal
~50%
common
~50%
Advisable
saquinavir
Normal
~100%
Normal
~100%
Not neccessary
sulfadiazine
Normal
~100%
Normal
~100%
Not neccessary
sulfamethazine
Normal
~100%
Normal
~100%
Not neccessary
sulfapyridine
Normal
~100%
Normal
~100%
Not neccessary
telithromycin
Normal
~100%
Normal
~100%
Not neccessary
terbinafine (FDA!)
Normal
~0%
common
0%
Advisable
voriconazole (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
Sleeping pills and tranquillizers (sedatives)
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
flunitrazapam
Normal
~100%
Normal
~100%
Not neccessary
hexobarbital
Normal
~100%
Normal
~100%
Not neccessary
melatonin
Normal
~100%
Normal
~100%
Not neccessary
methylphenobarbital
Normal
~100%
Normal
~100%
Not neccessary
Sleeping pills (soporifics)
midazolam
likely higher
~100%
Normal
~100%
Not neccessary
nitrazepam
Normal
~100%
Normal
~100%
Not neccessary
promethazine
Normal
~0%
common
0%
Advisable
triazolam
Normal
~100%
Normal
~100%
Not neccessary
zaleplon
Normal
~100%
Normal
~100%
Not neccessary
zolpidem
Normal
~99%
Normal
~100%
Not neccessary
zopiclone
Normal
~100%
Normal
~100%
Not neccessary
Page 17 of 180
Drugs for traveling sickness (antiemetic) Drugs for easing the feeling of sickness
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
aprepitant
Normal
~100%
Normal
~100%
Not neccessary
dolasetron
Normal
~0%
common
0%
Advisable
domperidone
Normal
~100%
Normal
~100%
Not neccessary
metoclopramide
Normal
~0%
common
0%
Advisable
Anti-cancer drugs (chemotherapy) Drugs for the treatment and prevention of cancer
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
anastrozole
Normal
~100%
Normal
~100%
Not neccessary
cyclophosphamide
likely higher
~100%
Normal
~100%
Not neccessary
docetaxel
Normal
~100%
Normal
~100%
Not neccessary
doxorubicin
Normal
~100%
Normal
~100%
Not neccessary
erlotinib
Normal
~100%
Normal
~100%
Not neccessary
etoposide
Normal
~100%
Normal
~100%
Not neccessary
gefitinib
Normal
~100%
Normal
~100%
Not neccessary
ifosfamide
likely higher
~100%
Normal
~100%
Not neccessary
imatinib
likely higher
~100%
Normal
~100%
Not neccessary
nilutamide
Normal
~100%
Normal
~100%
Not neccessary
paclitaxel
Normal
~100%
Normal
~100%
Not neccessary
sorafenib
Normal
~100%
Normal
~100%
Not neccessary
sunitinib
likely higher
~100%
Normal
~100%
Not neccessary
tamoxifen (FDA!)
likely higher
~10%
common
0%
Advisable
temsirolimus
Normal
~100%
Normal
~100%
Not neccessary
teniposide
Normal
~100%
Normal
~100%
Not neccessary
vemurafenib
Normal
~100%
Normal
~100%
Not neccessary
vinblastine
Normal
~100%
Normal
~100%
Not neccessary
vincristine
Normal
~50%
common
~50%
Advisable
vindesine
Normal
~100%
Normal
~100%
Not neccessary
Blood thinners (anticoagulant) Drugs for the treatment of thrombosis
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
clopidogrel
likely higher
~100%
Normal
~100%
Not neccessary
prasugrel
Normal
~100%
Normal
~100%
Not neccessary
r-warfarin (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
s-warfarin (FDA!)
Normal
~100%
Normal
5-7mg/day
Not neccessary
ticagrelor
Normal
~100%
Normal
~100%
Not neccessary
Page 18 of 180
Beta blockers Drugs for the treatment of high blood pressure, cardiac insufficiency and cardiac arrhythmia
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
alprenolol
Normal
~0%
common
0%
Advisable
carvedilol (FDA!)
Normal
~20%
common
~20%
Advisable
cilostazol
Normal
~100%
Normal
~100%
Not neccessary
debrisoquine
Normal
~0%
common
0%
Advisable
eplerenone
Normal
~100%
Normal
~100%
Not neccessary
hydralazine (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
isosorbide-dinitrate (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
metoprolol (FDA!)
Normal
~0%
common
0%
Advisable
nebivolol
Normal
~0%
common
0%
Advisable
perhexiline
Normal
~0%
common
0%
Advisable
propranolol (FDA!)
Normal
~20%
common
~20%
Advisable
s-metoprolol
Normal
~0%
common
0%
Advisable
timolol
Normal
~0%
common
0%
Advisable
Drugs for heart problems (anti-arrhythmic) Drugs for the treatment of heart problems
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amiodarone
Normal
~100%
Normal
~100%
Not neccessary
dronedarone
Normal
~100%
Normal
~100%
Not neccessary
encainide
Normal
~0%
common
0%
Advisable
flecainide
Normal
~0%
common
0%
Advisable
mexiletine
Normal
~0%
common
0%
Advisable
procainamide
Normal
~100%
Normal
~100%
Not neccessary
propafenone (FDA!)
likely higher
~40%
common
~50%
Advisable
quinidine (FDA!)
Normal
~33%
common
~20%
Advisable
sparteine
Normal
~0%
common
0%
Advisable
Cholesterol-lowering drugs (Statins) Drugs for lowering cholesterol
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
atorvastatin
Normal
~100%
Normal
~100%
Not neccessary
cerivastatin
Normal
~100%
Normal
~100%
Not neccessary
lescol
Normal
~100%
Normal
~100%
Not neccessary
lovastatin
likely higher
~100%
Normal
~100%
Not neccessary
Page 19 of 180
Anti-inflammatory drugs (anti-rheumatic) Drugs for the treatment of joint diseases
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
aceclofenac
Normal
~100%
Normal
~100%
Not neccessary
budesonide
Normal
~100%
Normal
~100%
Not neccessary
celecoxib
Normal
~100%
Normal
~100%
Not neccessary
dexamethasone
Normal
~100%
Normal
~100%
Not neccessary
diclofenac
Normal
~100%
Normal
~100%
Not neccessary
flurbiprofen
Normal
~100%
Normal
~100%
Not neccessary
hydrocortisone
Normal
~100%
Normal
~100%
Not neccessary
ibuprofen
Normal
~100%
Normal
~100%
Not neccessary
indomethacin
Normal
~100%
Normal
~100%
Not neccessary
lornoxicam
Normal
~100%
Normal
~100%
Not neccessary
meloxicam
Normal
~100%
Normal
~100%
Not neccessary
naproxen
Normal
~100%
Normal
~100%
Not neccessary
piroxicam
Normal
~100%
Normal
~100%
Not neccessary
sulfasalazine
Normal
~100%
Normal
~100%
Not neccessary
suprofen
Normal
~100%
Normal
~100%
Not neccessary
tenoxicam
Normal
~100%
Normal
~100%
Not neccessary
Drugs for high blood pressure (antihypertensive) Drugs for the treatment of high blood pressure, cardiac insufficiency and cardiac arrhythmia
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amlodipine
Normal
~100%
Normal
~100%
Not neccessary
atacand
likely higher
~100%
Normal
~100%
Not neccessary
bosentan
Normal
~100%
Normal
~100%
Not neccessary
candesartan
Normal
~100%
Normal
~100%
Not neccessary
diltiazem
Normal
~100%
Normal
~100%
Not neccessary
felodipine
Normal
~100%
Normal
~100%
Not neccessary
irbesartan
Normal
~100%
Normal
~100%
Not neccessary
lercanidipine
Normal
~100%
Normal
~100%
Not neccessary
losartan
likely higher
~100%
Normal
~100%
Not neccessary
nifedipine
Normal
~100%
Normal
~100%
Not neccessary
nisoldipine
Normal
~100%
Normal
~100%
Not neccessary
nitrendipine
Normal
~100%
Normal
~100%
Not neccessary
verapamil
Normal
~100%
Normal
~100%
Not neccessary
Page 20 of 180
Diabetes drugs (anti-diabetic) Drugs for diabetes type 2
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amaryl
Normal
~100%
Normal
~100%
Not neccessary
chlorpropamide
Normal
~100%
Normal
~100%
Not neccessary
diabeta
Normal
~100%
Normal
~100%
Not neccessary
glibenclamide
somewhat lower
~100%
Normal
~100%
Not neccessary
glimepiride
Normal
~100%
Normal
~100%
Not neccessary
glipizide
Normal
~100%
Normal
~100%
Not neccessary
nateglinide
Normal
~100%
Normal
~100%
Not neccessary
phenformin
Normal
~0%
common
0%
Advisable
rosiglitazone
Normal
~100%
Normal
~100%
Not neccessary
starlix
Normal
~100%
Normal
~100%
Not neccessary
tolbutamide
Normal
~100%
Normal
~100%
Not neccessary
Drugs for the treatment of Alzheimer's disease
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
donepezil
Normal
~80%
common
~100%
Not neccessary
galantamine (FDA!)
Normal
~0%
common
0%
Advisable
tacrine
Normal
~100%
Normal
~100%
Not neccessary
Painkillers
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
alfentanil
Normal
~100%
Normal
~100%
Not neccessary
buprenorphine
Normal
~100%
Normal
~100%
Not neccessary
codeine (FDA!)
likely higher
~20%
common
~20%
Advisable
enflurane
Normal
~100%
Normal
~100%
Not neccessary
fentanyl
Normal
~100%
Normal
~100%
Not neccessary
halothane
Normal
~100%
Normal
~100%
Not neccessary
hydrocodone
Normal
~0%
common
0%
Advisable
isoflurane
Normal
~100%
Normal
~100%
Not neccessary
levacetylmethadol
likely higher
~100%
Normal
~100%
Not neccessary
lidocaine
Normal
~100%
Normal
~100%
Not neccessary
Alzheimer's drugs
Painkillers (analgesics)
methadone
Normal
~90%
Normal
~100%
Not neccessary
methoxyflurane
Normal
~100%
Normal
~100%
Not neccessary
oxycodone
Normal
~0%
common
0%
Advisable
paracetamol
Normal
~100%
Normal
~100%
Not neccessary
phenacetin
Normal
~100%
Normal
~100%
Not neccessary
ropivacaine
Normal
~100%
Normal
~100%
Not neccessary
sevoflurane
Normal
~100%
Normal
~100%
Not neccessary
tramadol (FDA!)
likely higher
~40%
common
~50%
Advisable
zolmitriptan
Normal
~100%
Normal
~100%
Not neccessary
Page 21 of 180
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
Page 22 of 180
SCIENCE
Pharmaco Sensor CYP2D6 - cytochrome P450, family 2, subfamily D, polypeptide 6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that is involved in the metabolism of drugs through oxidation or hydrolysis of various substrates. This process is strongly influenced by the genetic variant of the CYP2D6 gene or allele. RES
Genotype
POP
URM
9%
X
Result options Certain medications are metabolized too quickly, and the dosage has to be increased
EM
70% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
16% Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
5%
Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Zhou SF. et al. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009,48(11):689-723. St端ven et al. Rapid detection of CYP2D6 null alleles by long distance- and multiplex-polymerase chain reaction. Pharmacogenetics. 1996 Oct,6(5):417-21.
CYP2C9 - cytochrome P450, family 2, subfamily C, polypeptide 9 Cytochrome P450 2C9 (CYP2C9) enzyme is expressed mainly in the liver, where it is involved in the oxidation of xenobiotic and endogenous substances. CYP2C9 plays an important role in the metabolism of various drugs. Defects in the CYP2C6 gene are associated with a reduced enzyme activity. RES
Genotype
POP
Result options
X
EM
77% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
21% Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
2%
Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Van Booven D. et al. Cytochrome P450 2C9-CYP2C9 Pharmacogenetics and genomics (2010)
Page 23 of 180
VKORC - Vitamin K epoxide reductase complex (rs9923231) The vitamin K epoxide reductase-(VKOR) is a membrane protein in the ER (endoplasmic reticulum), and it is involved in the formation of blood clotting factors. The anticoagulant Warfarin inhibits the activity of the VKOR protein. This inhibition can be prevented by defects of the VKORC gene. RES
Genotype
POP
Result options
X
C/C
40% No dose adjustment for the blood thinner Warfarin
C/T
40% Dose adjustment (reduction) for the blood thinner Warfarin
T/T
20% Dose adjustment (reduction) for the blood thinner Warfarin
References Anderson J. L. et al. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation. 2007 Nov 27,116(22):2563-70 Flockhart D. A. et al. Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genet Med. 2008 Feb,10(2):139-50. International Warfarin Pharmacogenetics Consortium Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009 Feb 19,360(8):753-64.
CYP2C19 - cytochrome P450, family 2, subfamily C, polypeptide 19 The cytochrome P450 2C19 (CYP2C19) enzyme is involved in the oxidative metabolism of various drugs, such as: antidepressants, antipsychotics, tranquilizers and proton pump inhibitors. CYP2C19 provides an alternative metabolic pathway for CPY2D6. Defects in the CYP2C19 gene can increase, or decrease, the enzymatic activity. RES
Genotype
POP
Result options
X
EM
69% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
28% Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
3%
Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Sheffield L. J. et al. Clinical use of pharmacogenomic tests in 2009. Clin Biochem Rev. 2009 May,30(2):55-65. Hodgson K. et al. Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. J Psychopharmacol. 2014 Feb,28(2):133-41.
NAT2 - N-acetyltransferase 2 (arylamine N-acetyltransferase) The arylamine N-acetyltransferase 2 (NAT2) is involved in the detoxification from drugs and endogenous substances through acetylation. Toxic and carcinogenic substances are converted and can be eliminated. The polymorphisms can alter the enzymatic activity of the NAT2 protein. RES
Genotype
POP
Result options
X
EM
45% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
30% Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
25% Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Daly A. K. et al. Pharmacogenomics of adverse drug reactions. Genome Med. 2013 Jan 29,5(1):5. Barbieri R. B. et al. Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk. Clin Endocrinol (Oxf). 2013 Aug,79(2):288-93. Int. braz j urol. vol.30 no.4 Rio de Janeiro Jul., Aug. 2004, Rama D. Mittal, Daya S.L. Srivastava, Anil Mandhani
Page 24 of 180
CYP3A4 - cytochrome P450, family 3, subfamily A, polypeptide 4 The cytochrome P450 3A4 (CYP3A4) is expressed in the liver, and it is involved in the activation, or hydroxylation, of various drugs and endogenous substances. RES
Genotype
POP
Result options
X
EM
96% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
3%
Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
1%
Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Chiang TS et al. Enhancement of CYP3A4 Activity in Hep G2 Cells by Lentiviral Transfection of Hepatocyte Nuclear Factor-1 Alpha. PLoS One. 2014 Apr 14,9(4):e94885. Lee JS et al. Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes. Korean J Physiol Pharmacol. 2013 Dec,17(6):479-84. Okubo M et al. CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with reduced CYP3A4 protein level and function in human liver microsomes. J Toxicol Sci. 2013,38(3):349-54.
CYP3A5 - cytochrome P450, family 3, subfamily A, polypeptide 5 The cytochrome P450 3A5 (CYP3A5) is expressed in the liver, and it is involved in the activation, or hydroxylation, of various drugs and endogenous substances. RES
X
Genotype
POP
URM
1%
Result options Certain medications are metabolized too quickly, and the dosage has to be increased
RM
10% Certain medications are metabolized too quickly, and the dosage has to be increased
NM
89% Affected drugs are metabolized as normal
References Lee JS et al. Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes. Korean J Physiol Pharmacol. 2013 Dec,17(6):479-84. Roden Dan M et al. Pharmacogenomics: the genetics of variable drug responses Circulation (2011)
CYP2E1 - cytochrome P450, family 2, subfamily E, polypeptide 1 The cytochrome P450 2E1 (CYP2E1) is expressed in the liver, and it is involved in the activation, or hydroxylation, of various drugs and endogenous substances. RES
Genotype
POP
Result options
X
EM
97% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
2%
Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
1%
Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Sheng YJ et al. The association between CYP2E1 polymorphisms and hepatotoxicity due to anti-tuberculosis drugs: A meta-analysis. Infect Genet Evol. 2014 Jun,24:34-40. De Bock L. et al. Quantification of cytochrome 2E1 in human liver microsomes using a validated indirect ELISA. J Pharm Biomed Anal. 2014 Jan 25,88:536-41.
Page 25 of 180
CYP1A2 - cytochrome P450, family 1, subfamily A, polypeptide 2 CYP1A2 (cytochrome P450 1A2) is a heme protein- enzyme involved in various metabolic processes. It metabolizes various xenobiotics such as caffeine, aflatoxin B1 and medications like paracetamol. RES
Genotype URM
X
POP
Result options
14% Certain medications are metabolized too quickly, and the dosage has to be increased
EM
53% Drugs are metabolized by this enzyme as normal Prodrugs are activated by this enzyme as normal
IM
28% Drugs are metabolized by this enzyme at a slow rate Prodrugs can barely be activated by this enzyme
PM
5%
Drugs are metabolized by this enzyme at a very slow rate Prodrugs are activated by this enzyme as normal
References Hubacek JA. et al. Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations. Drug Metabol Drug Interact. 2014,29(1):29-36.
NOS1AP - Nitric oxide synthase 1 (neuronal) adaptor protein (rs10494366) The nitric oxide synthase 1 adaptor protein (NOS1AP) is an adapter protein which binds the signal molecule nNOS (neuronal nitric oxide synthase) with other molecules, facilitating their interaction. This NOS1AP polymorphism decreases the glucose-reducing effect of different drugs and is associated with an increased mortality rate. RES
Genotype
POP
Result options
T/T
30% The drug Glibenclamide is effective The drug Sulfonyluria is effective The drug Tolbutamide is less effective/mortality rate is increased when using this drug The drug Glimepiride less effective/mortality rate is increased when using this drug
G/T
44% The drug Glibenclamide is less effective/mortality rate is increased when using this drug The drug Sulfonyluria is less effective/mortality rate is increased when using this drug The drug Tolbutamide is effective The drug Glimepiride is effective
G/G
26% The drug Glibenclamide is less effective/mortality rate is increased when using this drug The drug Sulfonyluria is less effective/mortality rate is increased when using this drug The drug Tolbutamide is effective The drug Glimepiride is effective
X
References Tomรกs M et al. Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QT syndrome. JACC. 2010 Jun 15,55(24):2745-52. Treuer AV et al. NOS1AP modulates intracellular Ca(2+) in cardiac myocytes and is up-regulated in dystrophic cardiomyopathy. Int J Physiol Pathophysiol Pharmacol. 2014 Mar 13,6(1):37-46. eCollection 2014. Becker et al. Common variation in the NOS1AP gene is associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea. Pharmacogenet Genomics. 2008 Jul,18(7):591-7.
Page 26 of 180
HIV RESISTANCE SENSOR Risk of infection and optimized therapy • Assessment of the risk of infection when in contact with a virus • Analysis of the CCR5 gene, relevant for the infection • Analysis of more than 16 genetic variations, for the effect of more than 20 drugs • Better treatment success by optimized medical therapy
Prevention Early diagnosis Treatment
PHARMACO GENETICS
HIV - Human Immunodeficiency Virus The human immunodeficiency virus, also called HIV virus, has become widespread since the 1980s and has infected about 34 million people so far. The infection is usually present for years or decades without noticeable symptoms, until eventually the immune system is weakened, so that other infections invade the body and eventually cause death. A virus can be described as a self-replicating machine. It usually consists of just a few genes, which are surrounded by a protein capsule. The surface of this capsule has the property of binding to certain elements, the so-called receptors, of certain cells of the body, and then to convey his genes into the interior of the cell. There, depending on the type of virus, it copies its genes and sometimes incorporates them into the genome of the cells. The infected cell cannot differentiate between its own genes and the genes of the virus, and so it activates them all. Viral genes have different functions. Some of the genes produce the building blocks of the protein capsule, while others copy and carry the viral genes into the new empty capsules. The new viruses then leave the cell and infect new cells, where the same process repeats. Each form of virus infests only certain cells, since each virus needs specific receptors. In the case of HIV, these are the cells of the immune system. The receptors which are required by HIV viruses are CD4 and CCR5. For each of the receptors, a human gene explains to the cell how to build the receptors. About 20% of the population has a genetic variation in a CR5 gene (CCR5delta32) and therefore produces only about half of the CCR5 receptors. This leads to a lower surface for the virus and considerably reduces the risk of infection. About 1% of the population has this mutation in both CCR5 genes, and is therefore very highly resistant to HIV.
Since CCR5 is essential for HIV infection, a drug that blocks the CCR5 receptors has already been developed (maraviroc). Other medicines for HIV are trying to block the replication of the virus genes or to interfere in other ways in the cycle of the virus. Without medical treatment, the infection with HIV is usually fatal, within several years or decades. With drug therapy, however, HIV infection is similar to a chronic disease, and the majority of infected people have a normal life expectancy of over 70 years. Therefore, an effective therapy is of great importance. Due to genetic differences in the genes that convert drugs in the body, it is possible that certain drugs are either not activated or their efficacy is low, resulting in regular use of overdose. Therefore, a genetic matching of the conversion capability of HIV-related drugs is extremely important for the optimal therapy.
Page 28 of 180
PHARMACO GENETICS
Relevant genes for HIV An analysis of HIV-related genes determines the risk of HIV infection, estimates the progression of the disease, and helps in the optimization of drug therapy. Since there are many other sexually transmitted diseases besides HIV, having a certain resistance to HIV should not to be understood as a replacement for protection during sexual intercourse. Regardless of the genetic predisposition to HIV, the use of condoms in risky sexual intercourse is recommended.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
CCR5
rs333
G>del
G/G
-
-
-
RISK
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Based on your genetic profile your cells produce CCR5 receptors needed by the virus. Your infection risk in case of contact is the same as for the general population. Risk of HIV infection in case of contact VERY LOW
LOW
NORMAL
â–˛
Page 29 of 180
PHARMACO GENETICS
Prevention An analysis of HIV-related genes determines the risk of HIV infection, estimates the progression of the disease, and helps in the optimization of drug therapy. Since there are many other sexually transmitted diseases besides HIV, having a certain resistance to HIV should not to be understood as a replacement for protection during sexual intercourse. Regardless of the genetic predisposition to HIV, the use of condoms in risky sexual intercourse is recommended. Based on your genetic profile your cells produce CCR5 receptors needed by the virus. Your infection risk in case of contact is the same as for the general population.
Page 30 of 180
PHARMACO GENETICS
Effect on relevant drugs Your genetic profile has an impact on the effect of drugs prescribed for HIV and associated diseases. This information can help your doctor choose the correct dosage of the right medications to minimize side effects.
Drugs for Infections (antibiotics etc.) Medication to combat infections
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
caspofungin
Normal
~100%
Normal
~100%
Not neccessary
clarithromycin
Normal
~100%
Normal
~100%
Not neccessary
dapsone
Normal
~100%
Normal
~100%
Not neccessary
erythromycin
Normal
~100%
Normal
~100%
Not neccessary
indinavir
Normal
~100%
Normal
~100%
Not neccessary
isoniazid (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
itraconazole
Normal
~100%
Normal
~100%
Not neccessary
ketoconazole
Normal
~100%
Normal
~100%
Not neccessary
nelfinavir
Normal
~100%
Normal
~100%
Not neccessary
nevirapine
Normal
~100%
Normal
~100%
Not neccessary
proguanil
likely higher
~100%
Normal
~100%
Not neccessary
pyrazinamide (FDA!)
likely higher
~100%
Normal
~100%
Not neccessary
rifampin (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
ritonavir
Normal
~50%
common
~50%
Advisable
saquinavir
Normal
~100%
Normal
~100%
Not neccessary
sulfadiazine
Normal
~100%
Normal
~100%
Not neccessary
sulfamethazine
Normal
~100%
Normal
~100%
Not neccessary
sulfapyridine
Normal
~100%
Normal
~100%
Not neccessary
telithromycin
Normal
~100%
Normal
~100%
Not neccessary
terbinafine (FDA!)
Normal
~0%
common
0%
Advisable
voriconazole (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
Page 31 of 180
SCIENCE
HIV Sensor (HIV resistance) CCR5 - chemokine (C-C motif) receptor 5 (gene/pseudogene) (rs333) The chemokine receptor CCR5 is widespread in leukocytes and leucoplasts, and plays an important role in a variety of immunological processes. Also, CCR5 is an essential co-receptor in the sexual transmission of HIV, by allowing the settling of the HIV virus into cells. It has been shown that the so-called CCR5 Delta32 mutation has an effect on both HIV infection risk, as well as on the progression of the disease. RES
Genotype
X
G/G
POP
Result options
90% Normal risk of HIV infection by viral contact
G/DEL
9%
Lower risk of HIV (CCR5 HIV variant) infection by viral contact Slower progression of the disease
DEL/DEL
1%
Virtually no risk of HIV infection by viral contact (CCR5 HIV variant) Normal risk of HIV infection by CCR5-independent HIV variants
References Huang et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996 Nov:2(11):1240-3. Fellay et al. NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). Common genetic variation and the control of HIV-1 in humans. PLoS Genet. 2009 Dec:5(12) H端tter et al. Coregulation of HIV-1 dependency factors in individuals heterozygous to the CCR5-delta32 deletion. AIDS Res Ther. 2013 Nov 18:10(1):26. Agrawal et al. CCR5Delta32 protein expression and stability are critical for resistance to human immunodeficiency virus type 1 in vivo. J Virol. 2007 Aug:81(15):8041-9
Page 32 of 180
PROSTATE HEALTH SENSOR Effective prevention and treatment of prostate cancer • Genetic assessment of prostate cancer risk • Genetic assessment of the prostate hyperplasia risk • Extensive testing with more than 9 genetic variations • Analysis of 13 genetic variations, for the effect of 40 + relevant drugs • Effective preventive measures and timely early diagnosis • Better chances of recovery through optimal drug therapy • Change of lifestyle to reduce the risk of disease • Medical monitoring for optimal prevention
Prevention Early diagnosis Treatment
ANDROLOGY
Prostate The prostate is a sex gland. It lies below the bladder, near the beginning of the urethra, and is about the size and shape of a chestnut. It consists of several glands that produce a secretion that is discharged during ejaculation into the urethra, where it is mixed with the sperm. Thus, it plays an important role in reproduction. Unfortunately, the prostate is also associated with a number of diseases, some of which can be serious or even fatal. As a result, every man should undergo an annual examination of the prostate after the age of 45. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate gland caused by the abnormal proliferation of certain cells. The disease is very common and usually develops with age. The risk of an enlarged prostate depends on genetic and lifestyle factors. About 10-20% of men between age 50 and 59 have this condition, and 25-35% of men in between 60 and 69. In contrast to prostate cancer, the symptoms of prostate enlargement develop very rapidly. Typical symptoms are: pain during urination; frequent urination; difficult, long-lasting urination supported by abdominal pressure. If the bladder is significantly obstructed, urine may accumulate in the kidney, which can cause a life-threatening condition. An enlarged prostate can be treated either with medication, depending on the extent, or reduced surgically using a laser beam. However, the best option remains prevention. Since benign enlargement of the prostate is closely related to an unfortunate combination of genes and lifestyle, modifications in lifestyle can greatly reduce the risk of disease for genetically predisposed people. Prostate cancer is one of the most common cancers for men. About 15% of men will be diagnosed with prostate cancer at some point in life. In most cases, prostate cancer does not produce symptoms until it has progressed, and so it is usually detected only
at a later stage through symptoms such as urinary symptoms, bone pain, weight loss, and anemia. The main complaints arising are referring to urination disorders: delayed onset, a weak jet, drip or the interruption of the urinary stream during urination. Residual urine often remains in the bladder. Other frequently observed symptoms include: increased or predominantly nocturnal urination, frequent urination in small quantities, difficulty, or pain when urinating. Due to pressure damage to nerves of the sacrum area, erection problems may also occur. Visible blood in the urine or sperm is rare but significant. A prostate tumor does not cause discomfort, and so symptoms usually appear only after the tumor has spread to nearby lymph nodes or into the bones. At that point, the most common symptoms are pain in the spine and pelvis. In most cases, bone metastases are the predominant disease, and they are also the most common cause of death from prostate cancer. The advanced stage is often accompanied by anemia and weight loss. Prostate cancer can only be treated successfully before it has spread, so early detection is crucial for effective treatment. That is why men over the age of 45 should be tested annually for prostate cancer. Treatment options include surgery with complete removal of the prostate, radiation therapy, hormone therapy, and in some cases, chemotherapy. Page 34 of 180
If the cancer is treated early, before spreading to other tissues, the 5-year survival rate is approximately 90%. After the cancer spreads, the 5-years survival rate is only around 35%, which is why early detection is so important. The lifetime risk for the diagnosis of "prostate cancer" is about 11%. It is estimated that approximately 20% of patients with prostate cancer die. About half of the cases of prostate cancer are caused by genetic variations. Now it is possible to test these genes and to determine the personal risk prior to the occurrence of prostate cancer. If the risk is significantly increased, a preventive program can significantly reduce the risk of developing of the disease. Additionally, you can detect potential diseases at an early stage through a more intensive monitoring program and allow for its timely treatment. More serious and unpleasant consequences can be prevented in most cases.
Page 35 of 180
ANDROLOGY
Relevant genes for prostate Several genetic variations have been identified, which taken individually slightly increase or decrease the risk of prostate cancer. Taken together, they have a significant impact on the risk probability. The analysis of relevant genetic variations came to the following conclusion:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECTIV E
RISK
TCF2
rs4430796
G>A
G/G
1
-
-
-
LOC124685
rs1859962
T>G
T/T
1
-
-
-
8q24 region 2
rs16901979
C>A
C/C
1
-
-
-
8q24 region 3
rs6983267
T>G
T/T
1
-
-
-
8q24 Region 1
rs1447295
C>A
C/C
1
-
-
-
VDR
rs2107301
C>T
T/T
2.47
-
-
RISK
8q24
rs4242382
G>A
A/A
2.1
-
-
RISK
8q24
rs7837688
T>G
T/T
1
-
-
-
8q24
rs2011077
A>G
A/A
1
-
-
-
RNASEL
rs627928
G>T
G/G
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Page 36 of 180
Summary of effects Here you can see a summary of the impact your genetic variations have on your health and your body: ➤ Your risk of developing prostate cancer is lower than that of the general population. What is your risk of prostate cancer? LOW
AVERAGE RISK
HIGHER
▲
When are checkups recommended? FROM 45 YEARS
EARLIER
▲
Page 37 of 180
ANDROLOGY
Prevention Your disease risk is normal. You should follow the general rules of a healthy life and get a prostate exam every year from age 45 forward. In this way, the age-related (nongenetic) forms of prostate diseases can be recognized and treated in time.
Page 38 of 180
ANDROLOGY
Effect on relevant drugs Your genetic profile has an impact on the effect of drugs prescribed for prostate cancer and associated diseases. This information can help your doctor choose the correct dosage of the right medications to minimize side effects.
Painkillers (analgesics) Painkillers
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
alfentanil
Normal
~100%
Normal
~100%
Not neccessary
buprenorphine
Normal
~100%
Normal
~100%
Not neccessary
codeine (FDA!)
likely higher
~20%
common
~20%
Advisable
enflurane
Normal
~100%
Normal
~100%
Not neccessary
fentanyl
Normal
~100%
Normal
~100%
Not neccessary
halothane
Normal
~100%
Normal
~100%
Not neccessary
hydrocodone
Normal
~0%
common
0%
Advisable
isoflurane
Normal
~100%
Normal
~100%
Not neccessary
levacetylmethadol
likely higher
~100%
Normal
~100%
Not neccessary
lidocaine
Normal
~100%
Normal
~100%
Not neccessary
methadone
Normal
~90%
Normal
~100%
Not neccessary
methoxyflurane
Normal
~100%
Normal
~100%
Not neccessary
oxycodone
Normal
~0%
common
0%
Advisable
paracetamol
Normal
~100%
Normal
~100%
Not neccessary
phenacetin
Normal
~100%
Normal
~100%
Not neccessary
ropivacaine
Normal
~100%
Normal
~100%
Not neccessary
sevoflurane
Normal
~100%
Normal
~100%
Not neccessary
tramadol (FDA!)
likely higher
~40%
common
~50%
Advisable
zolmitriptan
Normal
~100%
Normal
~100%
Not neccessary
Adverse Reaction
recommended dose*
alternative?
Drugs for traveling sickness (antiemetic) Drugs for easing the feeling of sickness
effect
Breakdown
aprepitant
Normal
~100%
Normal
~100%
Not neccessary
dolasetron
Normal
~0%
common
0%
Advisable
domperidone
Normal
~100%
Normal
~100%
Not neccessary
metoclopramide
Normal
~0%
common
0%
Advisable
Page 39 of 180
Anti-cancer drugs (chemotherapy) Drugs for the treatment and prevention of cancer
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
anastrozole
Normal
~100%
Normal
~100%
Not neccessary
cyclophosphamide
likely higher
~100%
Normal
~100%
Not neccessary
docetaxel
Normal
~100%
Normal
~100%
Not neccessary
doxorubicin
Normal
~100%
Normal
~100%
Not neccessary
erlotinib
Normal
~100%
Normal
~100%
Not neccessary
etoposide
Normal
~100%
Normal
~100%
Not neccessary
gefitinib
Normal
~100%
Normal
~100%
Not neccessary
ifosfamide
likely higher
~100%
Normal
~100%
Not neccessary
imatinib
likely higher
~100%
Normal
~100%
Not neccessary
nilutamide
Normal
~100%
Normal
~100%
Not neccessary
paclitaxel
Normal
~100%
Normal
~100%
Not neccessary
sorafenib
Normal
~100%
Normal
~100%
Not neccessary
sunitinib
likely higher
~100%
Normal
~100%
Not neccessary
tamoxifen (FDA!)
likely higher
~10%
common
0%
Advisable
temsirolimus
Normal
~100%
Normal
~100%
Not neccessary
teniposide
Normal
~100%
Normal
~100%
Not neccessary
vemurafenib
Normal
~100%
Normal
~100%
Not neccessary
vinblastine
Normal
~100%
Normal
~100%
Not neccessary
vincristine
Normal
~50%
common
~50%
Advisable
vindesine
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
Page 40 of 180
SCIENCE
Prostate Health Sensor TCF2 - Transcription factor 2 (rs4430796) The transcription factor 2 (TCF-2 or HNF1B) forms a heterodimer with TCF1, and activates, or inhibits, the expression of different target genes. The polymorphism rs4430796 is associated with an increased risk of prostate cancer. RES
Genotype
POP
A/A
18%
A/G
56% No increased risk of prostate cancer
G/G
26% No increased risk of prostate cancer
X
Result options Increased risk of prostate cancer (OR: 1.4)
References Zheng et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Feb 28,358(9):910-9. Levin et al. Chromosome 17q12 variants contribute to risk of early-onset prostate cancer. Cancer Res. 2008 Aug 15,68(16):6492-5. Gudmundsson et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet. 2007 Aug,39(8):977-83.
LOC124685 - Myosin, light chain 6, alkali, smooth muscle and non-muscle pseudogene (rs1859962) A genome-wide association study has shown that the polymorphism rs1859962 on chromosome 17q24.3 is associated with an increased risk of prostate cancer. RES
Genotype
POP
Result options
X
T/T
24% No increased risk of prostate cancer
T/G
57% No increased risk of prostate cancer
G/G
19%
Increased risk of prostate cancer (OR: 1.28)
References Sun et al. Cumulative effect of five genetic variants on prostate cancer risk in multiple study populations. Prostate. 2008 Sep 1,68(12):1257-62. Levin et al. Chromosome 17q12 variants contribute to risk of early-onset prostate cancer. Cancer Res. 2008 Aug 15,68(16):6492-5. Zheng et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Feb 28,358(9):910-9
8q24 region 2 (rs16901979) Several studies have shown that different polymorphisms on 8q24 increase the risk of prostate cancer. RES
Genotype
POP
A/A
1%
Increased risk of prostate cancer (OR: 1.53)
A/C
5%
Increased risk of prostate cancer (OR: 1.53)
C/C
94% No increased risk of prostate cancer
X
Result options
References Zheng et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Feb 28,358(9):910-9 Cheng et al. 8q24 and prostate cancer: association with advanced disease and meta-analysis. Eur J Hum Genet. 2008 Apr,16(4):496-505. Levin et al. Chromosome 17q12 variants contribute to risk of early-onset prostate cancer. Cancer Res. 2008 Aug 15,68(16):6492-5.
Page 41 of 180
8q24 region 3 (rs6983267) Several studies have shown that different polymorphisms on 8q24 increase the risk of prostate cancer. RES
Genotype
POP
Result options
X
T/T
24% No increased risk of prostate cancer
T/G
55% Increased risk of prostate cancer (OR: 1.25)
G/G
21%
Increased risk of prostate cancer (OR: 1.25)
References Haiman et al. A common genetic risk factor for colorectal and prostate cancer. Nat Genet. 2007 Aug,39(8):954-6. Yeager et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May,39(5):645-9. Epub 2007 Apr 1. Zheng et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Feb 28,358(9):910-9. Cheng et al. 8q24 and prostate cancer: association with advanced disease and meta-analysis. Eur J Hum Genet. 2008 Apr,16(4):496-505.
8q24 region 1 (rs1447295) Several studies have shown that different polymorphisms on 8q24 increase the risk of prostate cancer. RES
Genotype
POP
A/A
1%
Increased risk of prostate cancer (OR: 1.22)
A/C
12%
Increased risk of prostate cancer (OR: 1.22)
C/C
87% No increased risk of prostate cancer
X
Result options
References Zheng et al. Association between two unlinked loci at 8q24 and prostate cancer risk among European Americans. J Natl Cancer Inst. 2007 Oct 17,99(20):1525-33. Epub 2007 Oct 9. Amundadottir et al. A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006 Jun,38(6):652-8. Epub 2006 May 7. Freedman et al. Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men. Proc Natl Acad Sci U S A. 2006 Sep 19,103(38):14068-73. Epub 2006 Aug 31.
VDR - vitamin D (1,25- dihydroxyvitamin D3) receptor (rs2107301) The VDR gene encodes the vitamin D receptor, part of the steroid receptors family. It is a transcription factor that regulates the activity of specific target genes, and thus affects the metabolism. The rs2107301 polymorphism is associated with an increased risk of prostate cancer. RES
Genotype
POP
Result options
X
T/T
8%
T/C
36% Increased risk of prostate cancer (OR: 1.11)
C/C
56% No increased risk of prostate cancer
Increased risk of prostate cancer (OR: 2.47)
References Sch채fer et al. No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case-control study. Arch Dermatol Res. 2012 Jul,304(5):353-61. Holt et al. Vitamin D pathway gene variants and prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 2009 Jun,18(6):1929-33. Holick et al. Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2007 Oct,16(10):1990-9.
Page 42 of 180
8q24 (rs4242382) Several studies have shown that different polymorphisms on 8q24 increase the risk of prostate cancer. RES
Genotype
POP
Result options
X
A/A
1%
Increased risk of prostate cancer (OR: 2.1)
A/G
14%
Increased risk of prostate cancer (OR: 1.91)
G/G
85% No increased risk of prostate cancer
References Zheng et al. Association between two unlinked loci at 8q24 and prostate cancer risk among European Americans. J Natl Cancer Inst. 2007 Oct 17,99(20):1525-33. Epub 2007 Oct 9. Zheng et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Feb 28,358(9):910-9. Fitzgerald et al. Analysis of recently identified prostate cancer susceptibility loci in a population-based study: associations with family history and clinical features. Clin Cancer Res. 2009 May 1,15(9):3231-7.
8q24 (rs7837688) Several studies have shown that different polymorphisms on 8q24 increase the risk of prostate cancer. RES
Genotype
POP
Result options
X
T/T
1%
No increased risk of prostate cancer
T/G
14%
Increased risk of prostate cancer (OR: 1.91)
G/G
85% Increased risk of prostate cancer (OR: 1.67)
References Zheng et al. Association between two unlinked loci at 8q24 and prostate cancer risk among European Americans. J Natl Cancer Inst. 2007 Oct 17,99(20):1525-33. Epub 2007 Oct 9. Zheng et al. Cumulative association of five genetic variants with prostate cancer. N Engl J Med. 2008 Feb 28,358(9):910-9. Lindstrom et al. Characterizing associations and SNP-environment interactions for GWAS-identified prostate cancer risk markers--results from BPC3. PLoS One. 2011 Feb 24,6(2):e17142.
8q24 (rs2011077) Several studies have shown that different polymorphisms on 8q24 increase the risk of prostate cancer. RES
Genotype
X
POP
Result options
A/A
4%
A/G
32% Increased risk of prostate cancer (OR: 2.4)
No increased risk of prostate cancer
G/G
64% Increased risk of prostate cancer (OR: 6.2)
References Ma et al. Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population. Int J Cancer. 2008 Dec 1,123(11):2574-9.
Page 43 of 180
RNASEL - Ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent) (rs627928) RNase L, encoded by the RNASEL gene, is a ribonuclease that metabolizes viral and cellular RNA. The rs627928 polymorphism is associated with an increased risk of prostate cancer. RES
Genotype
POP
T/T
15%
Increased risk of prostate cancer (OR: 1.4)
T/G
51%
Increased risk of prostate cancer (OR: 1.24)
G/G
34% No increased risk of prostate cancer
X
Result options
References Mi et al. An update analysis of two polymorphisms in encoding ribonuclease L gene and prostate cancer risk: involving 13,372 cases and 11,953 controls. Genes Nutr. 2011 Nov,6(4):397-402. Breyer et al. Genetic variants and prostate cancer risk: candidate replication and exploration of viral restriction genes. Cancer Epidemiol Biomarkers Prev. 2009 Jul,18(7):2137-44. Li et al. RNASEL gene polymorphisms and the risk of prostate cancer: a meta-analysis. Clin Cancer Res. 2006 Oct 1,12(19):5713-9.
Page 44 of 180
Prevention Early diagnosis Treatment
CARDIOVASCULAR SENSOR Prevention and treatment of lipid metabolism problems • Analysis of more than 18 genetic variations • Identify the predisposition to high cholesterol (HDL and LDL), homocysteine and triglyceride levels • Is Omega-3 beneficial for cholesterol? • Identify the predisposition to sudden cardiac death (long QT interval) • Suitable micronutrients and diet for prevention and treatment • Analysis of more than 17 genetic variations, for the effect of 26 + relevant drugs • Better chances of recovery through optimal drug therapy • Medical monitoring for optimal prevention
CARDIOVASCULAR SYSTEM
Cardiovascular Disease Cholesterol and triglycerides are vital fats our body uses to produce cell membranes, store energy, absorb fat-soluble vitamins and produce hormones. These fats are so essential that our body even produces cholesterol itself. This cholesterol is then transported and made available for cell growth all over the body via the bloodstream. In this manner, our body produces about 70% of the cholesterol it needs itself. The other 30% comes from what we eat. The amount of cholesterol in your bloodstream goes up after every meal. To control this, your body has strict regulatory processes that maintain your blood cholesterol at normal levels. If there is too much cholesterol in your bloodstream, your body transports HDL to your liver, which filters it from your blood, lowering your cholesterol level. However, the liver will release LDL cholesterol into your bloodstream, which increases your cholesterol level. High cholesterol levels may cause arteriosclerosis, and so a low cholesterol level helps you stay healthy. Because of this, HDL cholesterol--the kind transported to the liver--is called "good" cholesterol, whereas LDL cholesterol--which the liver emits into the bloodstream--is called "bad" cholesterol.
That is why it is important for your health to maintain a high HDL and a low LDL cholesterol level. A number of genes are responsible for regulating cholesterol and triglyceride levels or for increasing the risk of cardiovascular disease. If you carry an adverse trait in one or more of these genes, you should pay special attention to your fat intake and metabolism. Since diet is the most significant influence on your body's lipid metabolism, it is important to follow a diet tailored to your genes.
Page 46 of 180
Arrhythmia Long QT syndrome is a life-threatening disease that can lead to sudden cardiac death in people with otherwise perfect health. The heartbeat is triggered by a recurring electrical pulse, which propagates through the heart. The time to initiate a heartbeat up to the point at which the cells are ready for the next heartbeat, is called the QT interval. If this interval is particularly long, it increases the risk of symptoms such as paroxysmal tachycardia, arrhythmia, vertigo or loss of consciousness. In severe cases, such episodes end in cardiac arrest due to ventricular fibrillation. However, most people with this condition have no symptoms until a life-threatening condition develops. The symptoms usually occur during physical exertion or stressful situations. A resting ECG (a measurement of the heart rate in the resting state) and a gene analysis help to better identify the risk. A long QT interval is usually not noticeable: more than half of the patients with long QT syndrome experience no symptoms. When symptoms do occur, they are caused by potentially lifethreatening heart rhythm disorders that are signs of serious disease. Palpitations may be sustained (more than 30 seconds) or intermittent, and sometimes remain unnoticed depending on the following: the duration and pulse rate, body position and the general constitution, dizziness, loss of consciousness or even cardiac arrest. Thus, they may lead to sudden cardiac death. Since tachycardia occurs suddenly and usually during exercise or in stressful situations, the symptoms are often unexpected, and observed because they affect our general state of well-being. People with this genetic risk should take steps to minimize symptoms. The steps include medical heart rate monitoring in high-risk situations such as cardiovascular disease, diabetes, morbid obesity, age over 55 years, extreme physical activity, and taking certain medications. If a prolonged QT interval is diagnosed in these situations, medical treatment may be necessary. Thanks to genetic analysis, you can find out if you are in a risk group and take the necessary precautions. Serious consequences such as sudden death can usually be prevented. Page 47 of 180
CARDIOVASCULAR SYSTEM
Relevant genes for cardiovascular disease The scientific community has linked several genes and polymorphisms to a risk of various cardiovascular diseases. An analysis of these polymorphisms allows us to determine your genetic risk for these diseases as well as some other genetic traits linked to this disease.
Cardiovascular sensor (cardiovascular disease) SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
CHD13
rs8055236
G>T
T/G
-
-
-
RISK
CHDS8
rs1333049
G>C
G/G
-
-
-
-
APOA5
rs662799
-1131T>C
A/A
-
-
-
-
PON1
rs662
Q192R
A/A
-
-
-
-
PON1
rs854560
L55M
T/T
-
-
-
-
APOB
rs5742904
R3500Q
A/G
-
-
-
RISK
SREBF2
rs2228314
Gly595Ala
G/G
-
-
-
RISK
NOS3
Ins/Del Int. 4
Ins/Del Intron 4
Ins/Ins
-
-
-
-
NOS3
rs2070744
-786 T/C
C/C
-
-
-
RISK
NOS3
rs1799983
Glu298Asp
G/G
-
-
-
-
APOA1
rs670
-75G > A
A/G
-
RESPOND
-
RISK
MTRR
rs1801394
Ile22Met
G/A
-
-
-
RISK
MMP3
rs3025058
5A/6A
T/T
-
-
-
RISK
GJA4
rs1764391
Pro319Ser
C/C
-
-
-
RISK
ITGB3
rs5918
Leu33Pro
T/T
-
RESPOND
-
-
CETP
rs708272
Taq1(B1>B2)
C/C
-
-
-
RISK
MTHFR
rs1801133
C>T
T/T
-
RESPOND
-
RISK
APOE
rs429358
T>C
T/T
-
-
-
-
APOE
rs7412
T>C
T/T
-
-
-
-
ApoE type
combination
E2/E3/E4
E2/E2
-
RESPOND
-
-
NOS1AP
rs16847548
T>C
T/T
-
-
-
-
NOS1AP
rs12567209
G>A
G/G
-
-
-
-
NOS1AP
rs10494366
T>G
T/G
-
RESPOND
-
RISK
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Page 48 of 180
Summary of effects This analysis examines numerous genes that contribute to risks for several different cardiovascular conditions. Many of these risk variations are common, and almost everyone has some genes that increase the risk of cardiovascular disease. If you have an unusually small number of genes that increase risk, your genes may actually reduce your risk of developing cardiovascular disease. Here you can see a summary of the influence your genetic variations have on your health and body: ➤ ➤ ➤ ➤ ➤ ➤ ➤
Compared to the average person, you have a 3.6 -times higher risk of coronary heart disease You have a high predisposition for high LDL cholesterol levels You have a slight predisposition for high triglyceride levels Vitamin B2 lowers your homocysteine levels Omega-3 fatty acids improve your cholesterol levels Aspirin can be effective in preventing thrombosis in risk situations Predisposition for slightly lowered HDL cholesterol values
Your risk of coronary heart disease, atherosclerosis and heart attack PROTECTION
AVERAGE RISK
INCREASED
▲ Your LDL cholesterol levels are likely to be
The effect of omega-3 on HDL cholesterol
NORMAL
IMPROVEMENT
INCREASED
▲ Your HDL cholesterol levels are likely to be NORMAL
LOW
▲ Your triglyceride levels are likely to be NORMAL INCREASED
▲
▲
Your homocysteine levels are likely to be NORMAL INCREASED
Effect of vitamin B2 on homocysteine REDUCTION
DETERIORATION
Effect of aspirin on thrombosis (blood clots) PROTECTION NO EFFECT
▲
▲
NO
Risk of sudden cardiac death (QT) NORMAL
▲
▲
Page 49 of 180
INCREASED
CARDIOVASCULAR SYSTEM
Prevention You have an elevated risk for coronary disease, and so it is particularly important for you to take preventative measures to reduce your risk. You should take steps to keep your cholesterol and triglycerides within normal levels. Discuss this issue with your doctor, and start an observation program based on your doctor's recommendation. The preventive measures and treatment options for cholesterol and triglycerides are listed separately. Talk to your doctor about putting these measures into practice. Preventive measures ➤ Do sports or regular exercise. The best exercises are endurance sports (walking, Nordic walking, cycling, swimming, weight training, etc.), and watch your weight. Ideally, you should do at least 30 minutes of exercises, 5 days a week. ➤ Smoking greatly increases your risk for vascular disease along with its many other health effects. Quitting smoking is one of the most important ways to improve your health. ➤ Keep alcohol consumption low (no more than one alcoholic beverage per day). ➤ In general, eat low-fat meals (fish, poultry and lean meats are recommended, but fatty meats like sausages, bacon, and fat cheese should be reduced). ➤ You should also eat only low-fat dairy products, for example low-fat milk, low fat cheese and low-fat yogurt. ➤ Eat as little animal products as possible, and use mainly vegetable oils. ➤ Eat fruits and vegetables multiple times during the day.
Omega-3-fatty acids ➤ Omega-3 fatty acids are usually recommended for high cholesterol, but for certain genetic types it can also worsen HDL-cholesterol. Based on your genes, Omega-3 improves your cholesterol levels.
Medical treatment is recommended when changes to diet and exercise do not lower cholesterol and triglycerides to a normal level. There are multiple options: statins, bile acid binders, fibrates, niacin (vitamin B3), cholesterol synthesis and absorption inhibitors. Your doctor will decide which drug is suitable for you. It is particularly important to take action to prevent heart disease because treatments followed after symptoms develop can only slow down the progress of the disease.
QT interval and sudden cardiac death As you are predisposed to have a long QT interval, you should take the following precautions, to avoid more serious complications. For you, it is important to understand the situations that create risk and to monitor your heart closely.
If you are exposed to the following risk factors it is strongly recommended that you have a physician determine the length of the QT intervals: ➤ ➤ ➤ ➤
Ischemia (circulatory disorder) Diabetes type 2 (diabetes) Metabolic Syndrome (severe overweight) Age over 55
If you are engaged in vigorous or difficult physical labor, your electrolyte level will drop. During these Page 50 of 180
events, regular electrolyte level testing should be performed, to detect abnormalities and allow for timely treatment. Prior to the taking medication that can affect the QT interval, you should have a resting ECG should be performed. Talk to your doctor about your genetic risk and the medications you are taking. In the context of a possible pharmacogenetic investigation by our laboratory, due to a possible QT prolonging effect, these drugs may influence the results. Your doctor should assess this based on your QT interval.
The following drug groups might not be appropriate: ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤
Antiarrhythmics Antiasthmatic Aerosols Antidepressants Antimalarial drugs Fluoroquinolones Macrolides Tamoxifen
This includes the following active ingredients (arranged alphabetically): Albuterol, Albuterol, Alfuzosin, Amantadine, Amiodarone, Amiodarone, Amitriptyline, Amphetamine, Amphetamine, Arsenic trioxide, Astemizole, Atazanavir, Atomoxetine, Azithromycin, Bepridil, Chloral hydrate, Chloroquine, Chlorpromazine, Ciprofloxacin, Cisapride, Citalopram, Clarithromycin, Clomipramine, Clozapine, Desipramine, Dexmethylphenidate, Diphenhydramine, Diphenhydramine, Disopyramide, Dobutamine, Dofetilide, Dolasetron, Domperidone, Dopamine, Doxepin, Dronedarone, Droperidol, Ephedrine, Ephedrine, Epinephrine, Epinephrine, Erythromycin, Erythromycin, Felbamate, Fenfluramine, Flecainide, Fluconazole, Fluoxetine, Fluoxetine, Foscarnet, Fosphenytoin, Galantamine, Gatifloxacin, Gemifloxacin, Granisetron, Halofantrine, Haloperidol, Ibutilide, Imipramine, Indapamide, Isoproterenol, Isoproterenol, Isradipine, Itraconazole, Ketoconazole, Lapatinib, Lapatinib, Levalbuterol, Levofloxacin, Levomethadyl, Lisdexamfetamine, Lithium, Lithium, Mesoridazine, Metaproterenol, Metaproterenol, Methadone, Methadone, Methylphenidate, Methylphenidate, Mexiletine, Midodrine, Moexipril/HCTZ, Moxifloxacin, Nicardipine, Nilotinib, Norepinephrine, Nortriptyline, Octreotide, Ofloxacin, Ondansetron, Oxytocin, Paliperidone, Paroxetine, Pentamidine, Pentamidine, Perflutren lipid microspheres, Phentermine, Phentermine, Phenylephrine, Phenylpropanolamine, Phenylpropanolamine, Pimozide, Probucol, Procainamide, Procainamide, Protriptyline, Pseudoephedrine, Pseudoephedrine, Quetiapine, Quinidine, Quinidine, Ranolazine, Risperidone, Ritodrine, Ritonavir, Roxithromycin, Salmeterol, Sertindole, Sertindole, Sertraline, Sibutramine, Solifenacin, Sotalol, Sparfloxacin, Sunitinib, Tacrolimus, Tamoxifen, Telithromycin, Terbutaline, Terfenadine, Thioridazine, Tizanidine, Tolterodine, Tolterodine, Trazodone, Trimethoprim-Sulfa, TrimethoprimSulfa, Trimipramine, Vardenafil, Venlafaxine, Voriconazole, Ziprasidone
Attention: Never decide by yourself to discontinue a medically prescribed medication. Only a doctor can decide this.
Page 51 of 180
CARDIOVASCULAR SYSTEM
Effect on relevant drugs Your genetic profile has an impact on the effect of drugs prescribed for cardiovascular disease. This information can help your doctor choose the correct dosage of the right medications to minimize side effects.
Drugs for heart problems (anti-arrhythmic) Drugs for the treatment of heart problems
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amiodarone
Normal
~100%
Normal
~100%
Not neccessary
dronedarone
Normal
~100%
Normal
~100%
Not neccessary
encainide
Normal
~0%
common
0%
Advisable
flecainide
Normal
~0%
common
0%
Advisable
mexiletine
Normal
~0%
common
0%
Advisable
procainamide
Normal
~100%
Normal
~100%
Not neccessary
propafenone (FDA!)
likely higher
~40%
common
~50%
Advisable
quinidine (FDA!)
Normal
~33%
common
~20%
Advisable
sparteine
Normal
~0%
common
0%
Advisable
Drugs for the treatment of high blood pressure, cardiac insufficiency and cardiac arrhythmia
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
alprenolol
Normal
~0%
common
0%
Advisable
carvedilol (FDA!)
Normal
~20%
common
~20%
Advisable
cilostazol
Normal
~100%
Normal
~100%
Not neccessary
debrisoquine
Normal
~0%
common
0%
Advisable
eplerenone
Normal
~100%
Normal
~100%
Not neccessary
hydralazine (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
isosorbide-dinitrate (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
metoprolol (FDA!)
Normal
~0%
common
0%
Advisable
nebivolol
Normal
~0%
common
0%
Advisable
perhexiline
Normal
~0%
common
0%
Advisable
propranolol (FDA!)
Normal
~20%
common
~20%
Advisable
s-metoprolol
Normal
~0%
common
0%
Advisable
timolol
Normal
~0%
common
0%
Advisable
Beta blockers
Page 52 of 180
Cholesterol-lowering drugs (Statins) Drugs for lowering cholesterol
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
atorvastatin
Normal
~100%
Normal
~100%
Not neccessary
cerivastatin
Normal
~100%
Normal
~100%
Not neccessary
fluvastatin
Normal
~100%
Normal
~100%
Not neccessary
lescol
Normal
~100%
Normal
~100%
Not neccessary
lovastatin
likely higher
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
Page 53 of 180
SCIENCE
Cardiovascular Sensor CDH13 - Cadherin 13 (rs8055236) The CDH13 gene encodes a protein of the cadherin superfamily. The protein is localized on the cell membrane, and it is expressed, inter alia, in the heart, in the aortic wall, in neurons, and in the spinal cord. The polymorphism rs8055236 is associated with an increased risk of heart diseases. RES
Genotype
POP
T/T
2%
T/G
34% Increased risk of coronary heart disease (OR: 1.91)
G/G
64% Increased risk of coronary heart disease (OR: 2.23)
X
Result options No increased risk of disease
References The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Linnea M. Baudhuin. Genetics of coronary artery disease: focus on genome-wide association studies. Am J Transl Res. 2009, 1(3): 221–234.
CHDS8 - Coronary heart disease, susceptibility to, 8 (rs1333049) The polymorphism rs1333049 on gene CHDS8 (Coronary heart disease, susceptibility to, 8) has been repeatedly associated with an increased risk of heart diseases. RES
Genotype
POP
Result options
X
G/G
30% No increased risk of disease
G/C
50% Increased risk of coronary heart disease (OR: 1.47)
C/C
20% Increased risk of coronary heart disease (OR: 1.9)
References Bilguvar K. et al. Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet. 2008 Dec,40(12):1472-7. Helgadottir A. et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008 Feb,40(2):217-24. Helgadottir A. et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007 Jun 8,316(5830):1491-3. Karvanen J. et al. The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts. Genet Epidemiol. 2009 Apr,33(3):237-46.
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APOA5 - Apolipoprotein A-V (rs662799) The protein encoded by this gene is an apolipoprotein and an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of several lipoprotein fractions including VLDL, HDL, chylomicrons. It is believed that apoA-V affects lipoprotein metabolism by interacting with LDL-R gene family receptors. Studies have shown, that carriers of the G-Allele experience low weight gain when eating a fatty diet. RES
Genotype
POP
Result options
X
A/A
96% No increased risk of disease
A/G
3%
Increased risk of coronary heart disease (OR: 1.98)/atherosclerosis/heart attack Predisposition to low HDL cholesterol (the good cholesterol) Predisposition to elevated triglyceride levels
G/G
1%
Increased risk of coronary heart disease (OR: 1.98)/atherosclerosis/heart attack Predisposition to low HDL cholesterol (the good cholesterol) Predisposition to elevated triglyceride levels
References Aberle J. et al. A polymorphism in the apolipoprotein A5 gene is associated with weight loss after short-term diet. Clin Genet. 2005 Aug,68(2):152-4. Aouizerat B. E. et al. Genetic analysis of a polymorphism in the human apoA-V gene: effect on plasma lipids. J Lipid Res. 2003 Jun,44(6):1167-73. Dorfmeister B. et al. The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbeans with type 2 diabetes. Biochim Biophys Acta. 2007 Mar,1772(3):355-63.
PON1 - Paraoxonase 1 (rs662) Paraoxonase (PON1) is an antioxidant enzyme involved in the radical elimination and in the lipometabolism. The polymorphisms rs854560 and rs662 lead to a reduced catalytic activity, and an increased risk of cardiovascular diseases. RES
Genotype
POP
Result options
X
A/A
43% No increased risk of disease
G/A
47% Increased risk of coronary heart disease/atherosclerosis/heart attack
G/G
10% Increased risk of coronary heart disease/atherosclerosis/heart attack
References Regieli et al. Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention. J Am Coll Cardiol. 2009 Sep 29,54(14):1238-45. Hassan et al. The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects. Mol Cell Biochem. 2013 Aug,380(1-2):121-8.
PON1 - Paraoxonase 1 (rs854560) Paraoxonase (PON1) is an antioxidant enzyme involved in the radical elimination and in the lipometabolism. The polymorphisms rs854560 and rs662 lead to a reduced catalytic activity, and an increased risk of cardiovascular diseases. RES
Genotype
POP
Result options
X
T/T
18%
A/T
46% Increased risk of coronary heart disease/atherosclerosis/heart attack
A/A
36% Increased risk of coronary heart disease/atherosclerosis/heart attack
No increased risk of disease
References Regieli et al. Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention. J Am Coll Cardiol. 2009 Sep 29,54(14):1238-45
Page 55 of 180
APOB R3500Q - Apolipoprotein B (rs5742904) Apolipoprotein B (ApoB) is the major protein component of the LDL proteins (low density lipoprotein), which are responsible for the transport of the cholesterol in the blood. As such, APOB regulates the LDL concentration in the organism. Rs5742904 polymorphism leads to an increased LDL cholesterol levels. RES
Genotype G/G
X
POP
Result options
98% No increased risk of disease
A/G
1%
Significantly increased risk of coronary heart disease/atherosclerosis/heart attack Significantly increased risk of elevated LDL cholesterol levels (familial Hypercholesterolemia)
A/A
1%
Significantly increased risk of coronary heart disease/atherosclerosis/heart attack Significantly increased risk of elevated LDL cholesterol levels (familial Hypercholesterolemia)
References Real et al. Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population. Eur J Hum Genet. 2003 Dec,11(12):959-65. Meriùo-Ibarra et al. Screening of APOB gene mutations in subjects with clinical diagnosis of familial hypercholesterolemia. Hum Biol. 2005 Oct,77(5):663-73. Haiqing et al. Familial Defective Apolipoprotein B-100 and Increased Low-Density Lipoprotein Cholesterol and Coronary Artery Calcification in the Old Order Amish. Arch Intern Med. Nov 8, 2010, 170(20): 1850–1855. Castillo et al. The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical diagnosis of familial hypercholesterolemia. Atherosclerosis. 2002 Nov,165(1):127-35.
SREBF2 - Sterol regulatory element binding transcription factor 2 (rs2228314) SREBF2 or SREBP2 (sterol regulatory element-binding protein 2) is a transcription factor involved in the regulation of the cholesterol metabolism. The cholesterol concentration is kept in balance through the control of the transcriptional activity of various target genes. RES
Genotype
POP
Result options
X
G/G
52% No increased risk of coronary heart disease Predisposition to elevated LDL cholesterol levels
G/C
45% Increased risk of coronary heart disease/atherosclerosis/heart attack No predisposition to elevated LDL cholesterol levels
C/C
3%
Increased risk of coronary heart disease/atherosclerosis/heart attack No predisposition to elevated LDL cholesterol levels
References Fan et al. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death. Published online Dec 30, 2008. Durst et al. The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients. Atherosclerosis. 2006 Dec,189(2):443-50.
Page 56 of 180
NOS3 - Nitric oxide synthase 3 (endothelial cell) (Ins/Del Int. 4) NO-synthases (NOS) are oxidases which catalyze the reaction of arginine to citrulline and nitric oxide. NOS3 is an endothelial nitric oxide synthase, predominantly expressed in endothelial cells on the inside of the blood vessels, where it indirectly adjusts the blood pressure and the afterload of the heart. Several polymorphisms in the NOS3 gene are associated with an increased risk of cardiovascular diseases. RES
Genotype
POP
Result options
X
Ins/Ins
76% No increased risk of disease
Ins/Del
22% No increased risk of disease
Del/Del
2%
Increased risk of coronary heart disease/atherosclerosis/heart attack
References Casas et al. Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23028 subjects. Circulation. 2004 Mar 23,109(11):1359-65.
NOS3 - Nitric oxide synthase 3 (endothelial cell) (rs2070744) RES
Genotype T/T
X
POP
Result options
98% No increased risk of disease
C/T
1%
No increased risk of disease
C/C
1%
Increased risk of coronary heart disease/atherosclerosis/heart attack
References Rossi et al. The T(-786)C endothelial nitric oxide synthase genotype predicts cardiovascular mortality in high-risk patients. J Am Coll Cardiol. 2006 Sep 19,48(6):1166-74.
NOS3 - Nitric oxide synthase 3 (endothelial cell) (rs1799983) RES
Genotype
POP
Result options
X
G/G
40% No increased risk of disease
G/T
52% Increased risk of coronary heart disease/atherosclerosis/heart attack
T/T
8%
Increased risk of coronary heart disease/atherosclerosis/heart attack
References Zhang et al. The G894T polymorphism on endothelial nitric oxide synthase gene is associated with increased coronary heart disease among Asia population: evidence from a Meta analysis. Thromb Res. 2012 Aug,130(2):192-7. Abdel-Aziz et al. Association of endothelial nitric oxide synthase gene polymorphisms with classical risk factors in development of premature coronary artery disease. Mol Biol Rep. 2013 Apr,40(4):3065-71.
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APOA1 - Apolipoprotein A-I (rs670) Apolipoprotein A1 (ApoA1) is the major protein component of HDL (high density lipoprotein) particles in the blood. These are responsible for the transport of the excess cholesterol to the liver, where it is further converted and eliminated. The polymorphism rs670 influences both the impact of polyunsaturated fatty acids on HDL cholesterol levels, as well as the risk of heart disease. RES
Genotype
X
POP
Result options
G/G
50% No increased risk of disease Polyunsaturated fatty acids (such as Omega 3) WORSEN the HDL cholesterol levels
A/G
38% Increased risk of coronary heart disease (OR: 1.47)/atherosclerosis/heart attack Polyunsaturated fatty acids (such as omega 3) improve the HDL cholesterol levels
A/A
12%
Increased risk of coronary heart disease (OR: 1.9)/atherosclerosis/heart attack Polyunsaturated fatty acids (such as omega 3) improve the HDL cholesterol levels
References Angotti E. et al. A polymorphism (G-->A transition) in the -78 position of the apolipoprotein A-I promoter increases transcription efficiency. J Biol Chem. 1994 Jul 1,269(26):17371-4. Juo S. H. et al. Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis. Am J Med Genet. 1999 Jan 29,82(3):235-41. Ordovas J. M. et al. Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am J Clin Nutr. 2002 Jan,75(1):38-46.
MTRR - 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (rs1801394) Methionine is a essential, sulfur containing proteinogenic amino acid. The synthesis of methionine is catalyzed by the methionine synthase enzyme, which in its turn requires homocysteine. The protein encoded by the MTRR gene (methionine synthase reductase) regenerates the inactive methionine synthase through methylation. RES
Genotype
X
POP
Result options
A/A
38% No increased risk of disease
A/G
34% Increased risk of coronary heart disease atherosclerosis/heart attack Predisposition to elevated homocysteine values
G/G
28% Increased risk of coronary heart disease atherosclerosis/heart attack Predisposition to elevated homocysteine values
References Cai et al. Genetic variant in MTRR, but not MTR, is associated with risk of congenital heart disease: an integrated meta-analysis. PLoS One. 2014 Mar 4,9(3):e89609. Olteanu et al. Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 2002 Nov 12,41(45):13378-85.
MMP3 - Matrix metallopeptidase 3 (stromelysin 1, progelatinase) (rs3025058) The matrix metalloproteinase-3 (MMP3), or Stromelysin1, is a zinc-dependent endopeptidase involved in the degradation of extracellular matrix components. As such, it plays an important role in the remodeling of tissues, wound healing, and inflammatory processes. The polymorphism (rs3025058) influences the risk of heart diseases. RES
Genotype
X
T/T T/Del Del/Del
POP
Result options
10% Increased risk of coronary heart disease (OR: 1.26)/atherosclerosis/heart attack 47% No increased risk of disease 43% Increased risk of coronary heart disease (OR: 1.26)/atherosclerosis/heart attack
References Abilleira et al. The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis. J Med Genet. 2006 Dec,43(12):897-901. Epub 2006 Aug 11. Zee et al. Genetic risk factors in recurrent venous thromboembolism: A multilocus, population-based, prospective approach. Clin Chim Acta. 2009 Apr,402(1-2):189-92.
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GJA4 - Gap junction protein, alpha 4, 37kDa (rs1764391) The GJA4 gene (Gap junction alpha-4 protein) belongs to the connexin gene family. These transmembrane proteins are components of the intercellular channels (the so-called gap junctions), which link the adjacent cells with each other, and facilitate the exchange of ions and small molecules. Gap junctions are mainly found in the heart muscle, in epithelial cells and in the retina. RES
Genotype
POP
T/T
14%
Increased risk of coronary heart disease (OR: 1.5)
C/T
41%
No increased risk of disease
C/C
45% Increased risk of coronary heart disease (OR: 1.5)
X
Result options
References Zhao et al . Cx37 C1019T Polymorphism May Contribute to the Pathogenesis of Coronary Heart Disease. Genet Test Mol Biomarkers. 2014 Apr 28.
ITGB3 - Integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61) (rs5918) The integrin beta 3 (ITGB3), or CD61, is a transmembrane protein involved in the signal transmission between cells and the extracellular matrix. It has been proven that carriers of the C allele (rs5918) have an increased risk of cardiovascular diseases. In addition, the polymorphism influences the blood-thinning effect of the aspirin drug. RES
Genotype
POP
Result options
X
T/T
74% No increased risk of disease Aspirin protects against thrombosis
T/C
24% Increased risk of coronary heart disease (OR: 1.5)/atherosclerosis/heart attack Aspirin provides no protection against thrombosis
C/C
2%
Increased risk of coronary heart disease (OR: 1.5)/atherosclerosis/heart attack Aspirin provides no protection against thrombosis
References Undas et al. Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation. 2001 Nov 27,104(22):2666-72. Weiss et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med. 1996 Apr 25,334(17):1090-4.
CETP - Cholesteryl ester transfer protein, plasma (rs708272) The cholesterol ester transfer protein (CETP) is a pore-forming protein involved in the lipoprotein metabolism. It is mainly expressed in the liver, and ensures the transfer of cholesterol esters from HDL to LDL or VLDL, in exchange for triglycerides. The polymorphism rs708272 influences the regulation of HDL cholesterol levels. RES
Genotype
X
POP
Result options
T/T
13%
C/T
70% Predisposition to bad HDL cholesterol values (the good cholesterol)
No predisposition to bad HDL cholesterol values (the good cholesterol)
C/C
17%
Predisposition to bad HDL cholesterol values (the good cholesterol)
References Radovica et al. The association of common SNPs and haplotypes in CETP gene with HDL cholesterol levels in Latvian population. PLoS One. 2013 May 13,8(5):e64191. Agirbasli et al. Multi-locus candidate gene analyses of lipid levels in a pediatric Turkish cohort: lessons learned on LPL, CETP, LIPC, ABCA1, and SHBG. OMICS. 2013 Dec,17(12):636-45. Wang et al. CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population. Lipids Health Dis. 2013 Nov 27,12:176.
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MTHFR - Methylenetetrahydrofolate reductase (NAD(P)H) (rs1801133) The methylenetetrahydrofolate reductase (MTHFR) is involved in many metabolic pathways in the human body. In the homocysteine metabolism, it is responsible for the degradation of homocysteine to methionine. The rs1801133 polymorphism leads to a reduced enzymatic activity of methylenetetrahydrofolate reductase, and thus to an increased homocysteine level. RES
Genotype
POP
Result options
X
T/T
9%
C/T
44% Predisposition to elevated homocysteine values Vitamin DOES NOT lower the homocysteine levels
C/C
47% No predisposition to elevated homocysteine values Vitamin lowers the homocysteine levels
Predisposition to elevated homocysteine values Vitamin DOES NOT lower the homocysteine levels
References Ashfield-Watt P.A. et al. Methylenetetrahydrofolate reductase 677C-->T genotype modulates homocysteine responses to a folate-rich diet or a low-dose folic acid supplement: a randomized controlled trial. Am J Clin Nutr. 2002 Jul,76(1):180-6. Bønaa K.H. et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006 Apr 13,354(15):1578-88. Lewis S. J. et al. Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ. 2005 Nov 5,331(7524):1053.
APOE - apolipoprotein E (E2/E3/E4) APOE (apolipoprotein E) metabolizes triglyceride-rich lipoprotein constituents, and plays a central role in the lipid metabolism. The ApoE gene is present in three common types, which are called allele E2, E3 and E4. The E4 allele is associated with an increased risk of heart disease and Alzheimer. RES
Genotype
POP
X
E2/E2
1%
No increased risk of coronary heart disease/atherosclerosis/heart attack No predisposition to elevated LDL cholesterol levels Predisposition to elevated triglyceride levels
E2/E3
6%
Increased risk of coronary heart disease/atherosclerosis/heart attack No predisposition to elevated LDL cholesterol levels Predisposition to elevated triglyceride levels
E3/E3
66% No increased risk of coronary heart disease/atherosclerosis/heart attack No predisposition to elevated LDL cholesterol levels No predisposition to elevated triglyceride levels
E2/E4
2%
E3/E4
24% Increased risk of coronary heart disease/atherosclerosis/heart attack Predisposition to elevated LDL cholesterol levels Predisposition to elevated triglyceride levels
E4/E4
1%
Result options
Increased risk of coronary heart disease/atherosclerosis/heart attack Predisposition to elevated LDL cholesterol levels Predisposition to elevated triglyceride levels
Increased risk of coronary heart disease/atherosclerosis/heart attack Predisposition to elevated LDL cholesterol levels Predisposition to elevated triglyceride levels
References Muendlein A et al. Synergistic effects of the apolipoprotein E epsilon3/epsilon2/epsilon4, the cholesteryl ester transfer protein TaqIB, and the apolipoprotein C3 -482 C>T polymorphisms on their association with coronary artery disease. Atherosclerosis. 2008 Jul,199(1):179-86. Burman D et al. Relationship of the ApoE polymorphism to plasma lipid traits among South Asians, Chinese, and Europeans living in Canada. Atherosclerosis. 2009 Mar,203(1):192-200. Roberto Elosua et al. Association of APOE genotype with carotid atherosclerosis in men and women the Framingham Heart Study. October 2004 The Journal of Lipid Research, 45, 1868-1875. Dallongeville et al. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis. J Lipid Res. 1992 Apr,33(4):447-54. Breslow et al. Genetic Basis of Lipoprotein Disorders. Circulation. 1995 Jan 15,91(2):505-12. Davignon et al. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988 Jan-Feb,8(1):1-21. Cubrilo-Turek et al. Apolipoprotein E genotypes and metabolic risk factors for coronary heart disease in middle-aged women. Coll Antropol. 1998 Jun,22(1):149-55.
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NOS1AP - Nitric oxide synthase 1 (neuronal) adaptor protein (rs16847548) The nitric oxide synthase 1 adaptor protein (NOS1AP) is an adapter protein which binds the signal molecule nNOS (neuronal nitric oxide synthase) with other molecules, facilitating their interaction. NOS1AP polymorphisms are associated with a prolonged QT interval, and an increased risk of sudden cardiac death. RES
Genotype
X
T/T
74% No increased risk of sudden cardiac death
T/C
25% Increased risk of sudden cardiac death (OR: 1.3)
C/C
POP
1%
Result options
Increased risk of sudden cardiac death (OR: 2.6)
References Arking et al. Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population. PLoS One. 2009,4(1):e4333. Crotti et al.NOS1AP is a genetic modifier of the long-QT syndrome. Circulation. 2009 Oct 27,120(17):1657-63. Kao et al. Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. Circulation. 2009 Feb 24,119(7):940-51.
NOS1AP - Nitric oxide synthase 1 (neuronal) adaptor protein (rs12567209) The nitric oxide synthase 1 adaptor protein (NOS1AP) is an adapter protein which binds the signal molecule nNOS (neuronal nitric oxide synthase) with other molecules, facilitating their interaction. NOS1AP polymorphisms are associated with a prolonged QT interval, and an increased risk of sudden cardiac death. RES
Genotype
POP
Result options
X
G/G
85% No increased risk of sudden cardiac death
A/G
14%
Protection against sudden cardiac death (OR: 0.51)
A/A
1%
Increased risk of sudden cardiac death (OR: 1.31)
References Kao et al. Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations. Circulation. 2009 Feb 24,119(7):940-51. Liu et al. A common NOS1AP genetic polymorphism, rs12567209 G>A, is associated with sudden cardiac death in patients with chronic heart failure in the Chinese Han population. J Card Fail. 2014 Apr,20(4):244-51. Eijgelsheim et al. Genetic variation in NOS1AP is associated with sudden cardiac death: evidence from the Rotterdam Study. Hum Mol Genet. Nov 1, 2009, 18(21): 4213–4218.
NOS1AP - Nitric oxide synthase 1 (neuronal) adaptor protein (rs10494366) The nitric oxide synthase 1 adaptor protein (NOS1AP) is an adapter protein which binds the signal molecule nNOS (neuronal nitric oxide synthase) with other molecules, facilitating their interaction. NOS1AP polymorphisms are associated with a prolonged QT interval, and an increased risk of sudden cardiac death. RES
Genotype
X
POP
Result options
G/G
10% Predisposition to increased QT-interval duration (+ 4 to 7,9 ms)
G/T
48% Predisposition to increased QT-interval duration (+ 1,7 to 4,6 ms)
T/T
42% No Predisposition to increased QT-interval duration
References Aarnoudse et al. Common NOS1AP variants are associated with a prolonged QTc interval in the Rotterdam Study. Circulation. 2007 Jul 3 Arking et al. A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nat Genet. 2006 Jun,38(6):644-51.
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Prevention Early diagnosis Treatment
THROMBO SENSOR Effectively prevent thrombosis • Possible diagnosis of an increased risk of thrombosis • Analysis of the 3 genes relevant for thrombosis • Analysis of 7 gene variations, for the effect of more than 4 relevant drugs • A thrombosis prevention program adapted to your genes • Increased protection against heart attack, stroke or pulmonary embolism • Warning of drugs that can trigger thrombosis • Better chances of recovery by optimal medical therapy • For women: Are the hormonal preparations dangerous for your health?
CARDIOVASCULAR SYSTEM
Thrombosis Thrombosis is a disease in which blood clots form in the bloodstream. These clots can clog certain blood vessels and reduce the flow of blood to the heart or to areas in the brain, leading to damage or even the death of the affected tissue. When the blood supply to part of the brain is cut off, a stroke occurs. If the blood supply to the heart is affected, it causes a heart attack. The most common form of thrombosis is a reduction of blood circulation in the legs by a blood clot. The danger here is that, if the clots dissolve, they can move and restrict the blood flow to the brain, the heart or the lungs. Genetic screening tests for the detection of a risk of thrombosis are unfortunately rarely performed, and since there are no noticeable symptoms until the occurrence of thrombosis, most people do not know that they are genetically predisposed.
if you know your genetic health risk, you can take preemptive measures, and, in most cases, even prevent the occurrence of thrombosis.
Therefore, a genetic predisposition is usually not detected until after the occurrence of thrombosis; this, however, may have fatal consequences. Genetic screening tests are still far too rarely performed, although they will allow one to be aware of the increased risk, and take the necessary preemptive measures, in some cases even allowing him to avoid the disease altogether. Several genes prevent the formation of blood clots in the veins. If one of these genes is defective, it cannot perform its task, and the risk of forming a blood clot increases significantly. Everyone has two genes of each type, and about one in twenty people carries a defect in at least one gene, thus being a carrier with an approximately 8- fold higher risk of thrombosis than the general population. About one in 200 people carries an error in both genes of a genotype, and has a 80 -fold higher thrombosis risk. Having defective genes does not necessary mean the patient will suffer from thrombosis, because only a fraction of those affected also develop the disease. Other factors also strongly contribute, such as obesity, bed rest and inactivity, prolonged air travel, contraceptive pill, pregnancy, etc. . This is why this genetic testing is so important; Page 63 of 180
CARDIOVASCULAR SYSTEM
Relevant genes for thrombosis Three genetic variations have been identified that can significantly increase the risk of thrombosis. Through an analysis of these three polymorphisms, the risk of developing a thrombosis can be determined, and reduced with specific preventive measures. The following genes have an impact on your risk of thrombosis:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
Factor-V
rs6025
G>A
G/G
1
-
-
-
Factor-II
rs1799963
G>A
G/G
1
-
-
-
PAI1
rs1799889
G>del
G/G
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
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Summary of effects Certain genes are responsible for preventing blood clotting in the blood vessels. Variations in these genes may interfere with this process, and therefore increase the risk of the formation of a blood clot, and, subsequently, thrombosis. Here you can see a summary of the impact that genetic variations have on your health and your body: ➤ Your risk of developing venous thrombosis is not increased ➤ Your risk of developing arterial thrombosis is the same as for the general population. Your risk of developing thrombosis NORMAL
INCREASED
▲
Risk of venous thrombosis NORMAL
INCREASED
▲ Risk of arterial thrombosis NORMAL
INCREASED
▲
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CARDIOVASCULAR SYSTEM
Prevention Based on your genetic profile, you have no increased risk of thrombosis. Your risk is the same as for the general population, and no special precautions are necessary. Even people with no genetic predisposition to thrombosis can still be affected by it. Therefore, the following preventative measures should be taken by everyone. Staying still for a long periods of time can lead to the formation of a clot. This can happen when a person is in bed for a long period because of sickness or after surgery Long intervals without moving, and even during prolonged sitting in a car or plane during long-distance traveil. These may lead to impaired blood flow that fosters the formation of a blood clot. To prevent this, take regular breaks during long trips, or walk in the plane to stretch your legs. Other risk factors for thrombosis include obesity and pregnancy, which both increase pressure in the veins. Smoking and an unhealthy diet are also risk factors for thrombosis.
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CARDIOVASCULAR SYSTEM
Effect on relevant drugs Your genetic profile has an impact on the effect of drugs prescribed for thrombosis and associated diseases. This information can help your doctor choose the correct dosage of the right medications to minimize side effects.
Blood thinners (anticoagulant) Drugs for the treatment of thrombosis
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
clopidogrel
likely higher
~100%
Normal
~100%
Not neccessary
prasugrel
Normal
~100%
Normal
~100%
Not neccessary
rwarfarin (FDA!)
Normal
~100%
Normal
~100%
Not neccessary
swarfarin (FDA!)
Normal
~100%
Normal
5-7%
Not neccessary
ticagrelor
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
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SCIENCE
Thrombo Sensor Factor-V - Coagulation factor V (proaccelerin, labile factor) (rs6025) The so-called factor V Leiden mutation is a genetically transmitted clotting defect, associated with an increased risk of thrombosis. This defect inhibits the degradation of factor V and the protein retains its coagulant effect. RES
Genotype
POP
A/A
1%
Increased risk of thrombosis (venous) (OR: 80!)
A/G
3%
Increased risk of thrombosis (venous) (OR: 7)
G/G
96% No increased risk of thrombosis (venous)
X
Result options
References Juul et al. Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Ann Intern Med. 2004 Mar 2,140(5):330-7. Brenner et al. Venous Thromboembolism Associated With Double Heterozygosity for R506Q Mutation of Factor V and for T298M Mutation of Protein C in a Large Family of a Previously Described Homozygous Protein C -Deficient Newborn With Massive Thrombosis: Blood. 1996 Aug 1,88(3):877-80. Zee et al. An Evaluation of Candidate Genes of Inflammation and Thrombosis in Relation to the Risk of Venous Thromboembolism. Circulation. Feb 2009, 2(1): 57–62. Rosendaal et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Br J Haematol. 2002 Mar,116(4):851-4. Kamphuisen et al. Thrombophilia screening: a matter of debate. Neth J Med. 2004,62:180-187. Ridker et al. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening, Jama 277 (1997) 1305-1307.
Factor-II - Coagulation factor II (thrombin) (rs1799963) The prothrombin mutation (factor II mutation) is a blood coagulant disorder. The risk of venous thrombosis is significantly increased by the polymorphism rs1799963, which allows the creation of too much clotting factor, prothrombin, in the blood. RES
Genotype
POP
A/A
1%
Increased risk of thrombosis (venous) (OR: 25)
A/G
3%
Increased risk of thrombosis (venous) (OR: 5)
G/G
96% No increased risk of thrombosis (venous)
X
Result options
References Zee et al. An Evaluation of Candidate Genes of Inflammation and Thrombosis in Relation to the Risk of Venous Thromboembolism: The Women’s Genome Health Study. Circ Cardiovasc Genet. Feb 2009, 2(1): 57–62. Foka et al. Factor V Leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. 2000 Feb,15(2):458-62. Andreassi et al. Prothrombin G20210A substitution and hormone therapy: indications for molecular screening, Clin Chem Lab Med 44 (2006) 514-521. Rosendaal et al. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol. 2002 Mar,116(4):851-4. Ye et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet. 2006 Feb 25,367(9511):651-8.
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PAI1 - Phosphoribosylanthranilate isomerase (rs1799889) Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein belonging to the group of serine protease inhibitors. It inhibits the fibrinolytic activity, by inactivating tPA and urokinase. A defect in the PAI1 gene leads to an increased transcription, and a higher concentration PAI1. This condition is associated with an increased risk of thrombosis. RES
Genotype
POP
Result options
Del/Del
24% Increased risk of thrombosis (arterial) (OR: 1.84)
Del/G
48% Increased risk of thrombosis (arterial) (OR: 1.83)
X
G/G
28% No increased risk of thrombosis (arterial)
References Tsantes et al. Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis. A meta-analysis. Thromb Haemost. 2007 Jun,97(6):907-13. Fernandes et al. 4G/5G polymorphism modulates PAI-1 circulating levels in obese women. Mol Cell Biochem. 2012 May,364(1-2):299-301. Gardemann et al. The 4G4G genotype of the plasminogen activator inhibitor 4G/5G gene polymorphism is associated with coronary atherosclerosis in patients at high risk for this disease. Thromb Haemost. 1999 Sep,82(3):1121-6.
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Prevention Early diagnosis Treatment
HYPERTENSION SENSOR Effective prevention and treatment of hypertension • Analysis of the three relevant genetic variations • Determination of genetic risk for high blood pressure • Adjusted screening program for lowering the blood pressure • Analysis of 7 gene variations, for the effect of 12+ relevant drugs • Better chances of recovery through optimal drug therapy
CARDIOVASCULAR SYSTEM
Hypertension Hypertension is a condition in which the blood pressure of the vascular system is chronically elevated. A chronic systolic blood pressure higher than 140 mmHg or a diastolic blood pressure greater than 90 mmHg (both measured after 10 minutes of sitting) are considered high blood pressure. This method of measurement is the current standard, because the blood pressure is often decreased after sitting down, and increased where physical activities are performed. This disease is very common and it is estimated that about 29% of the total population suffers from it. Blood pressure tends to increase with age. High blood pressure is particularly dangerous because it is not always noticeable. Some of the symptoms are morning headache, dizziness, nausea, nosebleeds, fatigue or insomnia. Most often, the disease progresses without symptoms, and it is only identified by the consequential damages, which is why it is also known as the "silent killer". Hypertension is a major risk factor in the development of atherosclerosis, or hardening of the arteries, especially if other risk factors such as severe obesity, diabetes, or elevated cholesterol or triglyceride levels occur. The resulting cardiovascular diseases, such as coronary heart disease (CHD), heart attack, heart failure, kidney failure, stroke, and vascular disease cause about 45% of deaths in men and 50% of deaths in women.
personal risk can take preventative measures to lower blood pressure and also speak to a doctor about their risk factors and condition. These steps can usually prevent the severe and often fatal diseases that are caused by long-term high blood pressure.
Apart from the increased risk of atherosclerosis, a permanently high blood pressure also causes damage to the heart muscle. The muscles are thicker and stiffer, so that the heart cannot easily relax in diastole (relaxation phase) and draw in the blood. This leads to a poorer filling of the heart, and the appearance of the heart failure symptoms. If left untreated, high blood pressure can damage the retina, causing blindness, or damage the kidneys to such an extent that kidney function is seriously reduced. Today, treatments exist to lower high blood pressure disease and alleviate the side effects. These modern drugs increase life expectancy and also tremendously improve the quality of life. Several genes are responsible for the regulation of blood pressure. Each one can carry a trait that increases the risk of developing high blood pressure. A person who is aware of their Page 71 of 180
CARDIOVASCULAR SYSTEM
Relevant genes for hypertension Three genetic variations have been identified that can significantly increase the risk of hypertension. Through an analysis of these three polymorphisms, the risk of developing hypertension can be determined, and reduced with specific preventive measures. The genetic analyses also helps in identifying the most effective therapy for lowering blood pressure. The following genes have an impact on your blood pressure:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
AGT
rs699
T>C
T/T
1
-
-
-
ADRB1
rs1801253
G>C
G/G
1
-
-
-
GNB3
rs5443
C>T
C/C
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects The analysed genes have an influence on your risk of high blood pressure, which can be also measured in the conventional way. Therefore, the benefit of this analysis is primarily to instantly determine the high blood pressure through regular examinations, and afterwards to properly treat it through lifestyle changes, and, if necessary, through the most effective therapy. Here you can see a summary of the impact your genetic variations have on your health and your body: ➤ You have no risk for elevated blood pressure. Your risk of hypertension NORMAL
INCREASED
â–˛
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CARDIOVASCULAR SYSTEM
Prevention Based on your genetic profile, you have no increased risk of suffering from high blood pressure. Therefore, you do not have to follow any specific preventive measures, but only the general guidelines of a healthy life. However, some people develop high blood pressure even without genetic defects, due to their own lifestyle. If you suffer from high blood pressure, despite your genetic profile, you can take the following precautionary measures.
Prevention In addition to genetic factors, environment and lifestyle play a crucial role in the development of high blood pressure. Therefore, it is important for you to understand the risk factors, and to change your lifestyle in order to avoid these risk factors. Giving up smoking is one of the most important ways to lower blood pressure. People who quit smoking in middle age have a similar life expectancy as those who never smoked. Smoking also affects the effectiveness of blood pressure medication. After 40 years of age, limit the amount of alcohol you consume, because alcohol has a direct impact on blood pressure and moderate or heavy drinking increases the risk of stroke. Light alcohol consumption of up to 250 mL of red wine a day may lower your blood pressure by 2-4mmHg. Obesity is an important risk factor and also increases your blood pressure. Therefore, reducing your weight will have a major impact and also lower your blood pressure. Losing 10kg of weight will lower your blood pressure with 5-20mmHg. Keep your BMI (Body Mass Index) under 25 to reduce your risk. Regular physical activity such as swimming, running or walking, even at low intensity, lowers blood pressure by 4 - 9mmHg . You can reduce blood pressure by getting 30 minutes of exercise several times a week. However, intense exercise is not recommended. Salt consumption is also an important risk factor for high blood pressure. You should limit sodium intake to 2500 mg or less. This can be expected to reduce blood pressure by 8mmHg. A healthy diet, with a large amount of fruit, vegetables, and fish and low in saturated fats can reduce blood pressure by 8-14mmHg.
Medical care and treatment Monitor your blood pressure to see how effective the changes you make are. Ask your doctor to measure your blood pressure regularly, or measure it yourself. Use the following guidelines to determine how often to check: Blood pressure
Systolic
Diastolic
Optimal blood pressure
under 120
under 80
Normal blood pressure
120-129
80-84
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High-normal blood pressure
130-139
85-89
Mild hypertension (stage 1)
140-159
90-99
Moder. hypertension (stage 2)
160-179
100-109
Severe hypertension (stage 3)
under 180
above 110
Isolated systolic hypertension
above 140
under 90
If your blood pressure is normal, check it every week and try to keep it within the normal range by following the measures described above. If your blood pressure is too high, take steps to lower it. If those measures do not lower your blood pressure to normal levels, talk to your doctor about possible medications to lower blood pressure. The choices are ACE inhibitors, AT1 antagonists, beta blockers, diuretics and calcium antagonists.
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CARDIOVASCULAR SYSTEM
Effect on relevant drugs Your genetic profile has an impact on the effect of drugs prescribed for high blood pressure and associated diseases. This information can help your doctor choose the correct dosage of the right medications to minimize side effects.
Drugs for high blood pressure (antihypertensive) Drugs for the treatment of high blood pressure, cardiac insufficiency and cardiac arrhythmia
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amlodipine
Normal
~100%
Normal
~100%
Not neccessary
atacand
likely higher
~100%
Normal
~100%
Not neccessary
bosentan
Normal
~100%
Normal
~100%
Not neccessary
candesartan
Normal
~100%
Normal
~100%
Not neccessary
diltiazem
Normal
~100%
Normal
~100%
Not neccessary
felodipine
Normal
~100%
Normal
~100%
Not neccessary
irbesartan
Normal
~100%
Normal
~100%
Not neccessary
lercanidipine
Normal
~100%
Normal
~100%
Not neccessary
losartan
likely higher
~100%
Normal
~100%
Not neccessary
nifedipine
Normal
~100%
Normal
~100%
Not neccessary
nisoldipine
Normal
~100%
Normal
~100%
Not neccessary
nitrendipine
Normal
~100%
Normal
~100%
Not neccessary
verapamil
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
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SCIENCE
Hypertension Sensor AGT - Angiotensinogen (serpin peptidase inhibitor, clade A, member 8) (rs699) The polymorphism rs699 in the angiotensinogen gene (AGT) leads to an increased concentration of angiotensinogen in the blood serum, and thus to a predisposition to high blood pressure. RES
Genotype
POP
Result options
X
T/T
37% No predisposition to high blood pressure/hypertension
T/C
43% Predisposition to high blood pressure/hypertension (OR: 1.2)
C/C
20% Predisposition to high blood pressure/hypertension (OR: 1.4)
References Nakajima et al.Nucleotide Diversity and Haplotype Structure of the Human Angiotensinogen Gene in Two Populations. Am J Hum Genet. Jan 2002, 70(1): 108–123. Jeunemaitre et al. Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2,71(1):169-80. Corvol et al. Molecular Genetics of Human Hypertension: Role of Angiotensinogen. Endocrine Reviews 18(5): 662–677.
ADRB1 - Adrenoceptor beta 1 (rs1801253) The β1-adrenoceptor protein encoded by the gene ADRB1 is the main adrenergic receptor of the human heart. It is mainly responsible for the effect of the adrenaline and the target structure of the beta-blockers. RES
Genotype
POP
Result options
X
G/G
14%
G/C
36% No predisposition to high blood pressure/hypertension
C/C
50% Predisposition to high blood pressure/hypertension (OR: 1.9)
No predisposition to high blood pressure/hypertension
References Johnson et al. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals. Hypertension. 2011 May,57(5):903-10.
GNB3 - Guanine nucleotide binding protein (G protein), beta polypeptide 3 (rs5443) G-proteins are signal transduction proteins, bonded to the inside of the cell membrane receptors, and involved in a variety of signaling pathways. The polymorphism rs5443 is associated with both high blood pressure, and with a predisposition to obesity. RES
Genotype
POP
Result options
X
C/C
33% No predisposition to high blood pressure/hypertension
C/T
57% Predisposition to high blood pressure/hypertension (OR: 6.1)
T/T
10% Predisposition to high blood pressure/hypertension (OR: 6.1)
References Siffert W. G-protein beta3 subunit 825T allele and hypertension. Curr Hypertens Rep. 2003 Feb,5(1):47-53.
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Prevention Early diagnosis Treatment
TOXO SENSOR Optimal support for the detoxification of toxins • Genetic analysis of the ability to detoxify pollutants • Detoxification of heavy metals, pesticides, weed agents, chemicals, soot and smoke • Analysis of cells' oxidative stress • Action program to reduce pollution • Micronutrient recommendation for filtering the heavy metals from the body • Analysis of 10 genetic variations which influence on the detoxification process • Effects of alcohol, coffee and addictive substances on your health • Adjustment of lifestyle for optimal health
METABOLISM
Detoxification In our daily lives, we are increasingly exposed to toxic pollutants that enter our bodies. Our bodies produce enzymes that recognize and neutralize many toxins. Certain genes are responsible for the production of these enzymes. Some traits in those genes limit your body's ability to effectively neutralize toxic substances. This significantly increases your risk for a variety of conditions caused by toxins. Therefore, a complete analysis of health risks must include these detoxification genes. Genetic traits limiting detoxification are very common among the European population and the body's detoxification ability varies greatly from person to person. These genetic differences help to explain why a 90-year-old heavy smoker may be in great health while another individual develops cancer at the age of 35. Each person has an individual genetic profile and it follows that each person should employ individual preventative measures to maintain good health.
Since different genes are responsible for the detoxification of certain toxic substances, the toxic substances categories are listed individually and your gene analysis results are interpreted per category.
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METABOLISM
Phase 1 Detoxification from ashes and soot Polycyclic aromatic hydrocarbons (PAHs) are common atmospheric pollutants produced mainly by burning fossil fuels such as coal, natural gas and oil. These pollutants enter the body via a myriad of paths: in food and drinking water, through the lungs when fumes or smoke are inhaled, and even directly through the skin. Once in our bodies, they can cause many different types of cancer, including lung cancer, laryngeal cancer, stomach cancer, intestinal cancer and bladder cancer. There are a number of detoxification genes that regulate enzymes that bind and neutralize toxic substances in your body. Some genetic traits reduce your body's capacity to produce these enzymes, and exposure to toxic substances increases your individual risk of cancer many times over. It is therefore very important for persons with inefficient detoxification enzymes to learn about their elevated risk in order to minimize their exposure to toxic substances and remain healthy. Your gene analysis shows the following:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
CYP1A1
rs4646903
T>C
T/T
1
-
-
-
CYP1B1
rs1056836
C>G
C/C
1
-
-
-
Summary of effects ➤ Phase 1 Detoxification is not limited ➤ Detoxification from ashes, smoke and soot (grilled foods) is not limited Effectiveness of Phase 1 Detoxification
Detoxification from ashes, soot (food), smoke
EFFECTIVE
EFFECTIVE
▲
INEFFECTIVE
▲
Page 79 of 180
INEFFECTIVE
METABOLISM
Phase 2 Detoxification from pesticides & heavy metals Detoxification genes 3 (GSTM1), 4 (GSTP1) and 5 (GSTT1) produce enzymes that bind and neutralize toxic substances often found in industrial solvents, herbicides, fungicides or insect repellent sprays, and also neutralize toxic heavy metals such as mercury, lead and cadmium. As long as they function efficiently, these genes ensure that these toxic substances effectively filtered out of your body. However, these genes can carry traits that prevent your body from adequately detoxifying. These traits significantly increase the risk of many different types of cancer and chronic fatigue syndrome.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
GSTM1
Zero allele
T=Zero allele
C/C
-
-
-
-
GSTT1
Zero allele
del=Zero allele
A/A
-
-
-
-
GSTP1
rs1695
A>G
A/A
-
-
-
-
Summary of effects ➤ Phase 2 Detoxification from pesticides, chemicals and heavy metals is not limited ➤ Your need for calcium, selenium, and zinc is average Effectiveness of Phase 2 Detoxification
Detoxification from heavy metals
EFFECTIVE
EFFECTIVE
INEFFECTIVE
▲
▲
Detoxification from pesticides, chemicals, fungicides, herbicides and insect repellent sprays EFFECTIVE
INEFFECTIVE
▲
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INEFFECTIVE
METABOLISM
Oxidative stress and free radicals Free radicals are created in cells during energy conversion. Free radicals are small, aggressive substances that damage the molecules around them through a chain reaction. They must be neutralized swiftly by the body. An imbalance between the creation and neutralization of free radicals is known as oxidative stress, which is one of the factors that affects the aging of your body and skin. Certain genes are responsible for the neutralization of free radicals. Unfortunately, many people have genetic traits that reduce their protection from free radicals. If your body does not have an innate ability to neutralize free radicals, you can consume higher levels of antioxidants – such as beta-carotene, vitamin C, vitamin E and acetylcysteine – that will increase your body's ability to resist oxidative stress. Coenzyme Q10 is a strong antioxidant that is capable of neutralizing free radicals, but only after being transformed into its active form, ubiquinol, by a certain gene. If this gene does not function, coenzyme Q10 cannot be transformed into ubiquinol and does nothing to protect against free radicals. It is therefore important to know if your body is capable of activating coenzyme Q10 to determine your need to take antioxidants.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
GSTM1
Zero allele
T=Zero allele
C/C
-
-
-
-
GSTT1
Zero allele
del=Zero allele
A/A
-
-
-
-
GSTP1
rs1695
A>G
A/A
-
-
-
-
SOD2
rs4880
Val16Ala
C/C
-
RESPOND
PROTECT.
-
GPX1
rs1050450
C>T
C/C
-
-
PROTECT.
-
NQO1
rs1800566
C>T
C/C
-
RESPOND
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
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Summary of effects ➤ ➤ ➤ ➤ ➤
You do not have an elevated level of oxidative stress in your cells You should consume the normally recommended amount of antioxidants Your body is able to activate inactive coenzyme Q10 Your diet or a dietary supplement can be a source of coenzyme Q10 Your need for selenium is average
Your oxidative stress in cells NORMAL
Recommended dose of antioxidants INCREASED
NORMAL
INCREASED
▲
▲
Activation of coenzyme Q10 to ubiquinol
Recommended antioxidant substance
POSSIBLE
COENZY. Q10
NOT POSSIBLE
▲
▲
Your daily requirement of selenium NORMAL INCREASED ▲
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VIT. C,E,A etc.
METABOLISM
Substances and risks We are all exposed to substances in our environment that affect us differently depending on our genes. Moderate consumption of alcohol poses no problem for most people, while others have a significantly elevated risk of alcohol dependence due to individual genetic variations. Illegal drugs also have different effects on our bodies. For instance, adolescents who smoke cannabis before the age of 16 have – in combination with a specific genetic variation – a 10-times higher risk of later developing schizophrenia. Your gene analysis shows the following:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
COMT
rs4680
G>A
G/G
-
-
-
RISK
CYP1A2
rs762551
C/A Pos. -163
A/A
-
-
PROTECT.
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
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Summary of effects ➤ You have a normal risk of alcoholism ➤ Consumption of cannabis before the age of 16 increases your risk of schizophrenia by 10.9 times higher ➤ Your body breaks down caffeine at a normale rate
Your risk of alcohol dependence NORMAL
INCREASED
▲ Your risk of schizophrenia (use of cannabis during adolescence) NORMAL INCREASED
How quickly is caffeine broken down? NORMAL ▲
▲
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SLOW
METABOLISM
Prevention Substances: You genes influence the effect that many substances, such as alcohol and caffeine, have on your body. Based on your genetic profile, you should be aware of the following traits: ALCOHOL Your genetic variations make you more likely to consume a large amount of alcohol, more likely to become alcoholic, and more likely to develop high blood pressure after drinking alcohol. Therefore, it would be advisable to consume little or no alcohol. SOY You have a genetic trait that reduces the activity of the COMT enzyme in your body. Soy contains substances that reduce this enzyme’s activity even further, and so you should avoid it. CAFFEINE Your body breaks down caffeine at a normale rate
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SCIENCE
Toxo Sensor CYP1A1 - Cytochrome P450, family 1, subfamily A, polypeptide 1 (rs4646903) The heme protein cytochrome P450-1A1 (CYP1A1) belongs to the group of phase I enzymes, and mediates the metabolism of environmental toxins and various xenobiotic substances. Defects in this gene can alter the enzymatic activity. RES
Genotype
X
T/T
62% Effective phase 1 detoxification of polycyclic aromatic hydrocarbons (PAHs) Effective detoxification of ash, soot and smoke
T/C
37% Limited phase 1 detoxification of polycyclic aromatic hydrocarbons (PAHs) (OR: 2.4) Limited detoxification of ash, soot and smoke
C/C
POP
1%
Result options
Limited phase 1 detoxification of polycyclic aromatic hydrocarbons (PAHs) (OR: 2.4) Limited detoxification of ash, soot and smoke
References Sun et al. Polymorphisms in Phase I and Phase II Metabolism Genes and Risk of Chronic Benzene Poisoning in a Chinese Occupational Population. Carcinogenesis. 2008 Dec,29(12):2325-9. Marinković et al. Polymorphisms of genes involved in polycyclic aromatic hydrocarbons’ biotransformation and atherosclerosis. Biochem Med (Zagreb). Oct 2013, 23(3): 255–265. Wright et al. Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer. Eur Respir J 2010, 35: 152–159. Jarvis et al. CYP1A1 MSPI (T6235C) gene polymorphism is associated with mortality in acute coronary syndrome patients. Clin Exp Pharmacol Physiol. 2010 Feb,37(2):193-8.
CYP1B1 - Cytochrome P450, family 1, subfamily B, polypeptide 1 (rs1056836) CYP1B1 belongs to the cytochrome P450 superfamily. This protein catalyzes reactions for detoxification of endogenous metabolites and exogenous toxic substances. This catalytic activity can be affected by polymorphisms. RES
Genotype
POP
Result options
X
C/C
32% Effective phase 1 detoxification of polycyclic aromatic hydrocarbons (PAHs) Effective detoxification of ash, soot and smoke
C/G
45% Limited phase 1 detoxification of polycyclic aromatic hydrocarbons (PAHs) (OR: 3.4) Limited detoxification of ash, soot and smoke
G/G
23% Limited phase 1 detoxification of polycyclic aromatic hydrocarbons (PAHs) (OR: 3.4) Limited detoxification of ash, soot and smoke
References Nock et al. Associations between Smoking, Polymorphisms in Polycyclic Aromatic Hydrocarbon (PAH) Metabolism and Conjugation Genes and PAH-DNA Adducts in Prostate Tumors Differ by Race. Cancer Epidemiol Biomarkers Prev. Jun 2007, 16(6): 1236–1245. Hanna et al. Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with functional differences in estrogen hydroxylation activity. Cancer Res. 2000 Jul 1,60(13):3440-4. Tang et al. Human CYP1B1 Leu432Val gene polymorphism: ethnic distribution in African-Americans, Caucasians and Chinese, oestradiol hydroxylase activity, and distribution in prostate cancer cases and controls. Pharmacogenetics. 2000 Dec,10(9):761-6.
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GSTM1 - glutathione S-transferase mu1 (null allele) The glutathione S-transferases are found in the liver and in the lymphocytes, and are involved in the detoxification of endogenous and exogenous substances. A defective GSTM1 gene reduces the enzymatic activity of the protein, which leads to a limited cellular detoxification. RES
Genotype
POP
Result options
X
C/C
10% Effective phase 2 detoxification Effective detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Good protection against oxidative stress / free radicals
C/T
38% Limited phase 2 detoxification Limited detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Limited protection against oxidative stress / free radicals
T/T
52% Limited phase 2 detoxification Limited detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Limited protection against oxidative stress / free radicals
References McWilliams et al. Glutathione S-transferase M1 (GSTM1) deficiency and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1995,4:589-594. Sreeja et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008,7(1):73-85. Funke et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009, 2009: 302047.
GSTP1 - Glutathione S-transferase pi 1 (rs1695) The glutathione S-transferases are found in the liver and in the lymphocytes, and are involved in the detoxification of endogenous and exogenous substances. The GSTP1 enzymes are involved in the metabolism of endogenous metabolites, and protect the cells against oxidative stress, similar with GSTM1 and GSTT1. RES
Genotype
POP
Result options
X
A/A
48% Effective phase 2 detoxification Effective detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Good protection against oxidative stress / free radicals
A/G
42% Limited phase 2 detoxification Limited detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Limited protection against oxidative stress / free radicals
G/G
10% Limited phase 2 detoxification Limited detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Limited protection against oxidative stress / free radicals
References Sreeja et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008,7(1):73-85. Miller et al. An association between glutathione S-transferase P1 gene polymorphism and younger age at onset of lung carcinoma. Cancer. 2006 Oct 1,107(7):1570-7. Funke et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009, 2009: 302047. St端cker et al. Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis. 2002 Sep, 23(9):1475-81.
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GSTT1 - glutathione S-transferase theta 1 (null allele) The glutathione S-transferases are found in the liver and in the lymphocytes, and are involved in the detoxification of endogenous and exogenous substances. A defective GSTM1 gene reduces the enzymatic activity of the protein, which leads to a limited cellular detoxification. RES
Genotype
X
A/A
POP
Result options
36% Effective phase 2 detoxification Effective detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Good protection against oxidative stress / free radicals
A/DEL
42% Limited phase 2 detoxification Limited detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Limited protection against oxidative stress / free radicals
DEL/DEL
22% Limited phase 2 detoxification Limited detoxification of pesticides, chemicals, fungicides, weed agents, insect sprays and heavy metals Limited protection against oxidative stress / free radicals
References Sreeja et al. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008,7(1):73-85. Funke et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009, 2009: 302047.
SOD2 - Superoxide dismutase 2, mitochondrial (rs4880) SOD2 encodes the superoxide dismutase enzyme 2 and it is involved in the degradation of reactive oxygen molecules (ROS), thus protecting the body against oxidative stress. Defects may affect the enzymatic activity of the SOD2 enzyme, resulting in a limited protection against the free radicals. RES
Genotype
POP
Result options
X
C/C
20% Good protection against oxidative stress / free radicals
C/T
53% Limited protection against oxidative stress / free radicals
T/T
27% Limited protection against oxidative stress / free radicals
References Sutton et al. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability. Pharmacogenet Genomics. 2005 May,15(5):311-9. Funke et al. Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy. J Cancer Epidemiol. 2009, 2009: 302047.
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GPX1 - Glutathione Peroxidase (rs1050450) The GPX gene encodes the enzyme glutathione peroxidase, which catalyzes the reduction of peroxides and hydrogen peroxide. Thus, GPX plays a role in protecting the body against oxidative stress. RES
Genotype
X
C/C
67% Good protection against oxidative stress / free radicals
C/T
26% Limited protection against oxidative stress / free radicals
T/T
POP
7%
Result options
Limited protection against oxidative stress / free radicals
References Tang et al. Association between the rs1050450 glutathione peroxidase-1 (C > T) gene variant and peripheral neuropathy in two independent samples of subjects with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2012 May,22(5):417-25. Bhatti et al. Lead exposure, polymorphisms in genes related to oxidative stress and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev. Jun 2009, 18(6): 1841–1848. Xiong et al. Association study between polymorphisms in selenoprotein genes and susceptibility to Kashin-Beck disease. Osteoarthritis Cartilage. 2010 Jun,18(6):817-24. Soerensen et al. The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old. Mech Ageing Dev. 2009 May,130(5):308-14. Steinbrecher et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev. 2010 Nov,19(11):2958-68. Chen et al. GPx-1 polymorphism (rs1050450) contributes to tumor susceptibility: evidence from meta-analysis. J Cancer Res Clin Oncol. 2011 Oct,137(10):1553-61. Karunasinghe et al. Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 2012 Apr,7(2):179-90. Hong et al. GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Mol Biol Rep. 2013 Feb,40(2):1801-12. Jablonska E et al. Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. Eur J Nutr. 2009 Sep,48(6):383-6.
NQO1 - NAD(P)H dehydrogenase, quinone 1 (rs1800566) The enzyme NAD(P)H dehydrogenase, encoded by the NQO1, is a so-called oxidoreductase, and catalyzes the oxidation of nicotinamide adenine dinucleotide (NAD). The polymorphism rs1800566 inhibits the enzymatic activity, and coenzyme Q10 cannot be converted into ubiquinol, or the conversion is slower than normal. RES
Genotype
X
C/C
66% The enzyme NQO1 effectively converts the coenzyme Q10 into the antioxidant ubiquinol.
C/T
30% The enzyme NQO1 converts the coenzyme Q10 into the antioxidant ubiquinol at a slower rate
T/T
POP
4%
Result options
The enzyme NQO1 cannot convert the coenzyme Q10 into the antioxidant ubiquinol
References Fischer et al. Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans. Published online Jul 21, 2011. Freriksen et al. Genetic polymorphism 609C>T in NAD(P)H:quinone oxidoreductase 1 enhances the risk of proximal colon cancer. J Hum Genet. 2014 May 15.
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COMT - Catechol-O-methyltransferase (rs4680) The enzyme catechol-O-methyltransferase (COMT) can inactivate various substances (epinephrine, norepinephrine, and dopamine) and perform the reduction. In addition, COMT may inhibit the effect of various drugs. The COMT rs4680 polymorphism is associated with psychological disorders, such as schizophrenia, eating disorders and alcoholism. RES
Genotype
X
POP
Result options
A/A
20% No effect Increased risk of alcoholism
A/G
55% Increased risk of schizophrenia when cannabis is consumed under the age of 16 years (OR: 2.5) Normal risk of alcoholism
G/G
25% Increased risk of schizophrenia when cannabis is consumed under the age of 16 years (OR: 10.9) Normal risk of alcoholism
References Caspi et al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry. 2005 May 15,57(10):1117-27. Kauhanen J et al. Association between the functional polymorphism of catechol-O-methyltransferase gene and alcohol consumption among social drinkers. Alcohol Clin Exp Res. 2000 Feb,24(2):135-9.
CYP1A2 - cytochrome P450, family 1, subfamily A, polypeptide 2 (rs762551) The heme protein cytochrome P450-1A2 (CYP1A2) belongs to the group of cytochrome P450 enzymes, and metabolizes various xenobiotic substances (including caffeine), medications, and estrogens. The polymorphism rs762551 is associated with the risk of breast cancer. RES
Genotype
POP
X
A/A
51%
A/C
42% Caffeine is broken down slowly Coffee consumption does not influence the appearance of breast cancer
C/C
7%
Result options Caffeine is broken down normally The consumption of 2 or more cups of coffee per day delays the appearance of breast cancer with approximately 7 years (59.8 years instead of 52.6 years).
Caffeine is broken down slowly Coffee consumption does not influence the appearance of breast cancer
References B책geman et al. Coffee consumption and CYP1A2*1F genotype modify age at breast cancer diagnosis and estrogen receptor status. Cancer Epidemiol Biomarkers Prev. 2008 Apr,17(4):895-901.
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DIABETES SENSOR Prevention and effective treatment of diabetes • Genetic evaluation of diabetes risk • Analysis of over 8 genes with influence on diabetes • Analysis of 11 genetic variations, for the effect of 15+ relevant drugs • Assessment of the risk for gestational diabetes • Assessment of the time (sooner or later) for insulin substitution requirements • Effectiveness determination of metformin, glibenclamid, tolbutamide and glimepiride • Medically supervised prevention program
Prevention Early diagnosis Treatment
METABOLISM
Diabetes Type 2 Diabetes is a common metabolic disease in which the body loses the ability to properly regulate blood sugar. The ability to regulate blood sugar declines somewhat with age, and almost one in ten people in the industrialized world suffers from diabetes. Sugar is the primary fuel for our cells. It is transported through the blood along with oxygen and other nutrients. High levels of blood sugar damage cells, and low levels prevent them from functioning properly. Therefore, the body has a mechanism that precisely regulates blood sugar levels and keeps it in the right range. When you consume a large amount of sugar, that sugar enters the bloodstream. After a certain point, the body begins to filter the sugar from the blood and stores it. If you go without eating for a long time, your body releases sugar from the reserve into the bloodstream. In this way, the blood sugar level remains constant and ensures that all cells are supplied with just the right amount of fuel. As we grow older, this regulatory process gradually becomes less exact. Certain risk factors, including lack of exercise, obesity, and certain genetic traits, accelerate this gradual decline in precision. In some people, blood sugar rises to levels that trigger a variety of physical ailments, some of which can be life-threatening. In this case, the condition is called diabetes type 2 and requires medical treatment. Diabetes is often accompanied by a great number of other ailments. High blood pressure, blood lipid disorders, neuropathy, blood vessel damage, kidney disease and even blindness are all common effects of untreated diabetes. In order to prevent these secondary conditions, a person with diabetes must maintain consistent and regular control of their blood sugar levels. A physician is usually able to perform a fasting blood glucose test or a glucose tolerance test to diagnose diabetes. In these tests, the patient drinks a large amount of sugary liquid and the doctor then measures the blood glucose levels,
which show how effectively the body regulates blood sugar. The treatment plan for diabetes depends on the level of blood sugar. In most cases, diet and exercise will keep diabetes in check. Sometimes oral medication will be prescribed, and in rare cases injections of insulin will become necessary. Diabetes type 2 is a lifestyle disease that is especially prevalent in developed countries, where large quantities of many kinds of food are available. Obesity is the most important risk factor for diabetes. Certain genetic traits that play a role in regulating blood sugar also increase the risk of diabetes in some individuals. By analysing relevant genes, your personal genetic risk of developing diabetes can be determined. Individuals with a high risk of diabetes can then follow specific preventative programs that will reduce their risk of developing the disease.
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METABOLISM
Genes associated with diabetes type 2 So far, scientists have identified several genetic traits that can increase the risk of developing type 2 diabetes. An analysis of all relevant traits allows us to determine your risk of diabetes as well as some other genetic traits linked to this disease. The following genes influence blood sugar regulation and are associated with the risk of diabetes type 2.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
TCF7L2
rs7903146
VS3C>T
C/T
1.65
RESPOND
-
RISK
HIGD1C
rs12304921
A>G
G/A
2.5
-
-
RISK
HHEX
rs1111875
A>G
A/A
1
-
-
-
IL6
rs1800795
G/C Pos. -174
G/G
1.51
RESPOND
-
RISK
IL10
rs1800872
C/A Pos. -592
C/C
1
-
-
-
PPARG
rs1801282
Pro12Ala
G/G
1
-
-
-
FTO
rs9939609
A/T
T/T
1
-
-
-
KCNJ11
rs5219
C>T
C/C
1
-
-
-
NOS1AP
rs10494366
T>G
T/G
-
RESPOND
-
RISK
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Several risk genes were analysed for the development of type 2 diabetes in this analysis, and many of the genetic traits that increase the risk of diabetes are fairly common. Thus, almost every person is affected by some level of genetic risk. You may carry more traits that increase your risk than an average person and have a higher risk of developing diabetes. It is also possible that you may carry fewer genes that increase the risk of diabetes, so you have a lower risk of developing diabetes. Here, you can see a summary of the influence that genetic variations have on your health and your body:
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➤ Compared to the optimal genetic profile, you have 1.1 -times higher risk of type 2 diabetes ➤ Metformin is more likely to prevent you from developing diabetes type 2 ➤ The drug glibenclamide is only moderately effective as a blood sugar reducer, but can be adequately metabolized by your body. ➤ The drug tolbutamide is an especially effective blood sugar reducer for you, and can be adequately metabolized by your body. ➤ If you develop type 2 diabetes, you are more likely to require insulin ➤ The drug glimepiride is especially effective as a blood sugar reducer, and can be adequately metabolized by your body. Your genetic risk of diabetes type 2 PROTECTION
AVERAGE RISK
INCREASED ▲
requiring insulin with DMT2 NORMAL
EARLIER ▲
Glibenclamide as a blood sugar reducer EFFECTIVE INEFFECTIVE ▲ Effectiveness of tolbutamide EFFECTIVE
INEFFECTIVE
Effectiveness of glimepiride EFFECTIVE
INEFFECTIVE
▲ Effectiveness of metformin for prevention NORMAL REDUCED ▲ Effectiveness of sulfonyluria EFFECTIVE
▲
INEFFECTIVE ▲
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METABOLISM
Prevention Your genetic analysis shows that you have an increased risk of developing diabetes type 2 and so we strongly recommend that you follow certain preventative measures. We recommend an annual checkup, including a glucose tolerance test, for people 45 and older. This test measures how your body reacts to sugar. Also, your blood sugar should be tested regularly so that diabetes can be detected earlier and treated properly. Complications associated with diabetes, such as high blood pressure and problems with blood lipids, can be prevented or treated if diabetes is detected early. It is also advisable to follow a low-calorie, high-fiber diet in order to maintain your blood sugar levels. Frequent exercise (at least 30 minutes 5 days a week) is healthy for everyone, and it is also an important way to reduce diabetes. Physical activity speeds up your metabolism and causes your body to remove sugar from the blood more quickly, which lowers your blood sugar level. Diet A low-calorie and high-fiber diet reduces blood sugar levels and the risk of prolonged hyperglycemia. Likewise, physical activity speeds up metabolism and lowers blood sugar levels. Proper nutrition is a critical prevention measure, and also very important for people already suffering from diabetes. A guide to a proper diet, based on the recommendations of the German Nutrition Society (DGE), reads as follows: (This diet should be adapted for people with allergies or food intolerance) ➤ A varied selection of nutrient-rich and energy-poor foods is the foundation of a healthy, balanced diet. ➤ Eat fruits and vegetables several times a day: fresh or briefly cooked fruits and vegetables contain a variety of vitamins, fiber, minerals and various phytochemicals such as carotenoids and flavonoids. ➤ Eat dairy products daily and fish twice a week. Meat, sausage and eggs should be consumed only in small quantities. Dairy products contain calcium, while iodine, selenium and omega-3 fatty acids are found in fish. Vitamins B1, B6 and B12 are found in meat, which is also a good source of iron. 300 - 600 g of red meat per week will add enough iron to the diet. ➤ Fat is very rich in energy and a high-fat diet will often lead to obesity. The intake of too many saturated fats increases the risk of lipid disorders, and can cause heart and circulatory diseases. If possible, use vegetable oils and fats such as canola and soybean oil, and pay attention to invisible fat, which is often found in meat, dairy products, pastry and confectionery, as well as in fast-food and processed products. ➤ Use small amounts of sugar and salt. Season with herbs and spices instead. Foods and beverages containing sugar should only be eaten occasionally. Use little salt when cooking (preferably with iodine and fluoride) and season with herbs and spices instead. ➤ Drink 1.5 L (50 oz) of liquid daily, not counting alcohol and coffee. Low-calorie beverages without added sugars are better, while alcohol should be consumed only occasionally and in small quantities. ➤ Prepare your food carefully. Cook at very low temperatures with little fat and for a short time in order to Page 95 of 180
retain the essential nutrients and to hinder the formation of harmful compounds. ➤ It is better to have five little meals as opposed to three large ones. Have smaller meals several times, and take your time while eating. Slow eating encourages versatile access and promotes satiety sensation. ➤ Watch your weight and get exercise. Being overweight increases the risk for diabetes, and should be prevented through a healthy diet and sufficient physical activity.
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METABOLISM
Effect on relevant drugs Your genetic profile has the following effects on drugs that are commonly prescribed for diabetes type 2 and associated diseases. This information should be considered as a possible warning of side effects and help your doctor to choose the right dosages. For drugs labelled "(FDA!)", the american "Food and Drug Administration" FDA has already issued warnings that genetic variations can lead to serious side effects.
Cholesterol-lowering drugs (Statins) Drugs for lowering cholesterol
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
atorvastatin
Normal
~100%
Normal
~100%
Not neccessary
cerivastatin
Normal
~100%
Normal
~100%
Not neccessary
fluvastatin
Normal
~100%
Normal
~100%
Not neccessary
lescol
Normal
~100%
Normal
~100%
Not neccessary
lovastatin
likely higher
~100%
Normal
~100%
Not neccessary
Diabetes drugs (anti-diabetic) Drugs for diabetes type 2
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amaryl
Normal
~100%
Normal
~100%
Not neccessary
chlorpropamide
Normal
~100%
Normal
~100%
Not neccessary
diabeta
Normal
~100%
Normal
~100%
Not neccessary
glibenclamide
somewhat lower
~100%
Normal
~100%
Not neccessary
glimepiride
Normal
~100%
Normal
~100%
Not neccessary
glipizide
Normal
~100%
Normal
~100%
Not neccessary
nateglinide
Normal
~100%
Normal
~100%
Not neccessary
phenformin
Normal
~0%
common
0%
Advisable
rosiglitazone
Normal
~100%
Normal
~100%
Not neccessary
starlix
Normal
~100%
Normal
~100%
Not neccessary
tolbutamide
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
Page 97 of 180
SCIENCE
Diabetes Sensor TCF7L2 - Transcription factor 7-like 2 (T-cell specific, HMG-box) (rs7903146) TCF7L2 (transcription factor 7-like 2) is a transcription factor which affects many different genes. The polymorphism rs7903146 is considered the most important genetic risk factor for type 2 diabetes. RES
Genotype
X
POP
Result options
C/C
55% No increased risk of type 2 diabetes mellitus Insulin substitutions should be taken in case of illness, as normally prescribed
C/T
35% Increased risk of type 2 diabetes mellitus (OR: 1.65) In case of diabetes, a prior insulin substitution treatment is necessary
T/T
10% Increased risk of type 2 diabetes mellitus (OR: 2.77) In case of diabetes, a prior insulin substitution treatment is necessary
References Lyssenko et al. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest. Aug 1, 2007, 117(8): 2155–2163. Cauchi et al. TCF7L2 genetic defect and type 2 diabetes. Curr Diab Rep. 2008 Apr,8(2):149-55. Bodhini et al. The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians. Metabolism. 2007 Sep,56(9):1174-8.
HIGD1C - HIG1 hypoxia inducible domain family, member 1C (rs12304921) A comprehensive study associated the polymorphism rs12304921 on HIGD1C gene with an increased risk of type 2 diabetes. RES
Genotype
X
POP
Result options
A/A
70% No increased risk of diabetes mellitus type 2.
G/A
27% Increased risk of type 2 diabetes mellitus (OR: 2.5)
G/G
3%
Increased risk of type 2 diabetes mellitus (OR: 1.94)
References The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007 Jun 7,447(7145):661-78.
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HHEX - Hematopoietically expressed homeobox (rs1111875) The HHEX gene encodes a transcription factor involved in many developmental processes. A genome-wide study has shown that carriers of the G allele have an increased risk of type 2 diabetes. RES
Genotype
POP
Result options
X
A/A
17%
G/A
50% Increased risk of type 2 diabetes mellitus (OR: 1.21)
G/G
33% Increased risk of type 2 diabetes mellitus (OR: 1.44)
No increased risk of diabetes mellitus type 2.
References van Vliet-Ostaptchouk et al. HHEX gene polymorphisms are associated with type 2 diabetes in the Dutch Breda cohort. Eur J Hum Genet. 2008 May,16(5):652-6 Omori et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008 Mar,57(3):791-5. Epub 2007 Dec 27. Furukawa et al. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2008 Jan,93(1):310-4.
IL6 - interleukin 6 (rs1800795) Interleukin-6 is one of the pro-inflammatory cytokines and it is an essential part of the immune response to inflammatory processes. The polymorphism rs1800795, located in the promoter region of the gene, alters the expression of the cytokine. Carriers of the C allele produce less IL6. RES
Genotype
X
POP
Result options
C/C
25% Protection against type 2 diabetes mellitus (OR: 0.91)
G/C
50% Protection against type 2 diabetes mellitus (OR: 0.91)
G/G
25% Increased risk of type 2 diabetes mellitus (OR: 1.51)
References Huth et al. IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants' data from 21 studies. Diabetes. 2006 Oct,55(10):2915-21. Illig et al. Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. J Clin Endocrinol Metab. 2004 Oct,89(10):5053-8. Fishman et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemiconset juvenile chronic arthritis. J Clin Invest. 1998 Oct 1,102(7):1369-76.
IL10 - Interleukin 10 (rs1800872) Interleukin-10 (IL10) is one of the anti-inflammatory cytokines and has numerous functions in the immune system. The polymorphism is associated with an increased risk of type 2 diabetes and increased resistance to insulin. RES
Genotype
X
C/C
48% No increased risk for type 2 diabetes mellitus No increased insulin resistance
C/A
45% No increased risk for type 2 diabetes mellitus No increased insulin resistance
A/A
POP
7%
Result options
Increased risk of type 2 diabetes mellitus (OR: 1.63) Increased insulin resistance (OR: 1.99)
References Bai et al. Association between interleukin 10 gene polymorphisms and risk of type 2 diabetes mellitus in a Chinese population. J Int Med Res. 2014 Apr 23. Scarpelli et al. Variants of the interleukin-10 promoter gene are associated with obesity and insulin resistance but not type 2 diabetes in caucasian italian subjects. Diabetes. 2006 May,55(5):1529-33.
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PPARG - Peroxisome proliferator-activated receptor gamma (rs1801282) Peroxisome proliferator-activated receptor gamma (PPAR-Îł or PPARG), also known as the glitazone receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor that in humans is encoded by the PPARG gene. PPARG regulates fatty acid storage and glucose metabolism. The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice fail to generate adipose tissue when fed a high-fat diet. RES
Genotype
POP
X
G/G
1%
Result options No increased risk of diabetes mellitus type 2.
G/C
22% Increased risk of type 2 diabetes mellitus (OR: 1.19)
C/C
77% Increased risk of type 2 diabetes mellitus (OR: 1:38)
References Gouda et al. The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. Am J Epidemiol. 2010 Mar 15,171(6):645-55. Altshuler et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000 Sep,26(1):76-80. Deeb et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998 Nov,20(3):284-7.
FTO - Fat mass and obesity associated (rs9939609) Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16. The amino acid sequence of the transcribed FTO protein shows high similarity with the enzyme AlkB which oxidatively demethylates DNA. Recombinant FTO protein was first discovered to catalyze demethylation of 3-methylthymine in single-stranded DNA, and 3-methyluridine in single-stranded RNA, with low efficiency. The nucleoside N6-methyladenosine, an abundant modification in RNA, was then found to be a major substrate of FTO. The FTO gene expression was also found to be significantly upregulated in the hypothalamus of rats after food deprivation and strongly negatively correlated with the expression of orexogenic galanin like peptide which is involved in the stimulation of food intake. RES
Genotype
POP
Result options
X
T/T
25% No increased risk of diabetes mellitus type 2.
T/A
57% Increased risk of type 2 diabetes mellitus (OR: 1.34)
A/A
18%
Increased risk of type 2 diabetes mellitus (OR: 1.68)
References Frayling et al. A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity. Science. May 11, 2007, 316(5826): 889–894. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007 Jun 7,447(7145):661-78. Hertel et al. Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia. 2008 Jun,51(6):971-7.
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KCNJ11 - Potassium inwardly-rectifying channel, subfamily J, member 11 (rs5219) The KCNJ11 gene (potassium inwardly rectifying-channel, subfamily J, member 11) is encoding the Kir2.6 protein, a subunit of the ATPsensitive potassium channels. These channels are located in the cell membrane, and can use the hormone insulin to regulate the glucose concentration in blood. A defect can lead to increased glucose levels, and thus an increased risk of diabetes. RES
Genotype
POP
Result options
X
C/C
58% No increased risk of diabetes mellitus type 2. The drug Metformin is effective
C/T
34% Increased risk of type 2 diabetes mellitus (OR: 1.23) The drug Metformin is less effective than normal
T/T
8%
Increased risk of type 2 diabetes mellitus (OR: 1.65) The drug Metformin is less effective than normal
References Florez et al. Type 2 Diabetes–Associated Missense Polymorphisms KCNJ11 E23K and ABCC8 A1369S Influence Progression to Diabetes and Response to Interventions in the Diabetes Prevention Program. Diabetes. Feb 2007, 56(2): 531–536. Zhou et al. The E23K variation in the KCNJ11 gene is associated with type 2 diabetes in Chinese and East Asian population. J Hum Genet. 2009 Jul,54(7):433-5. Omori et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008 Mar,57(3):791-5. Epub 2007 Dec 27. Florez et al. Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes. 2004 May,53(5):1360-8.
NOS1AP - Nitric oxide synthase 1 (neuronal) adaptor protein (rs10494366) The nitric oxide synthase 1 adaptor protein (NOS1AP) is an adapter protein which binds the signal molecule nNOS (neuronal nitric oxide synthase) with other molecules, facilitating their interaction. This NOS1AP polymorphism decreases the glucose-reducing effect of different drugs and is associated with an increased mortality rate. RES
Genotype
X
POP
Result options
T/T
30% The drug Glibenclamide is effective The drug Sulfonyluria is effective The drug Tolbutamide is less effective/mortality rate is increased when using this drug The drug Glimepiride less effective/mortality rate is increased when using this drug
G/T
44% The drug Glibenclamide is less effective/mortality rate is increased when using this drug The drug Sulfonyluria is less effective/mortality rate is increased when using this drug The drug Tolbutamide is effective The drug Glimepiride is effective
G/G
26% The drug Glibenclamide is less effective/mortality rate is increased when using this drug The drug Sulfonyluria is less effective/mortality rate is increased when using this drug The drug Tolbutamide is effective The drug Glimepiride is effective
References Tomás M et al. Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QT syndrome. JACC. 2010 Jun 15,55(24):2745-52. Treuer AV et al. NOS1AP modulates intracellular Ca(2+) in cardiac myocytes and is up-regulated in dystrophic cardiomyopathy. Int J Physiol Pathophysiol Pharmacol. 2014 Mar 13,6(1):37-46. eCollection 2014. Becker et al. Common variation in the NOS1AP gene is associated with reduced glucose-lowering effect and with increased mortality in users of sulfonylurea. Pharmacogenet Genomics. 2008 Jul,18(7):591-7.
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Prevention Early diagnosis Treatment
ALZHEIMER SENSOR Risk assessment, prevention and better treatment • Genetic evaluation of innate Alzheimer's risk • Analysis of the APOE-types for risk assessment • Adjusted screening program, which can delay the apparition of the disease with a number of years • Adapted diet for reducing the risk • Micronutrient recommendations for reducing the risk • Analysis of over 18 genetic variations, for the effect of over 20 drugs • More effective treatment through the optimal use of medications • Medically supervised prevention program
METABOLISM
Alzheimer's disease Alzheimer's disease (often simply called Alzheimer's) is a disease characterized by a progressive loss of certain brain cells. The cause of Alzheimer's is not fully understood. However, certain genetic traits have been clearly linked to a significantly increased risk of developing the disease. These traits cause abnormally folded proteins to accumulate in certain regions of the brain and allow for the development of large numbers of toxic molecules known as free radicals that damage brain cells. The damaged brain cells in affected regions of the brain slowly deteriorate. day objects. Irritability and aggression are common and as the disease progresses, the person becomes increasingly dependent on caregivers. Alzheimer's disease accounts for roughly 60 percent of the roughly 24 million diagnosed cases of dementia worldwide. The most common form affects individuals over the age of 65. Around 2% of 65-year-olds are affected whereas among 70-year-olds the figure rises to 3%. 6% of 75-year-olds and roughly 20% of 85-year-olds display symptoms of the disease.
Early signs of Alzheimer's can be detected as early as eight years before diagnosis. Examples of early symptoms include short term memory loss and difficulties with language as well as depression and apathy. The disease is often not recognized until the person develops noticeable learning disorders and short term memory loss increases while long term memory remains unaffected. In advanced stages, persons diagnosed with Alzheimer's completely lose even basic skills and abilities and eventually cease to recognize close friends and family or even day-to-
So far, the scientific community has not found a cure for Alzheimer's disease. However, there are a great number of preventative measures that can be effective for people with a genetic predisposition to Alzheimer's. Memory training, changes in lifestyle, an appropriate diet and controlling certain other conditions can all play an important role in preventing Alzheimer's. Measures such as these can delay the development of Alzheimer's for many years or even prevent it entirely. It is therefore especially important for persons who carry these genetic defects to learn about their risk and begin preventative measures as early as possible.
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METABOLISM
Genes associated with Alzheimer's disease A combination of two different polymorphisms plays a role in the development of Alzheimer's disease. There are combinations linked to a 15-times higher risk of Alzheimer's. Still other combinations are linked to a 30% reduction in the risk of Alzheimer's compared to the population average. Your gene analysis shows the following:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
APOE
rs429358
T>C
T/T
-
APOE
rs7412
T>C
T/T
-
ApoE type
combination
E2/E3/E4
E2/E2
0.7
RESPOND
PROTECT.
RISK
RESPOND
PROTECT.
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Here you can see a summary of the influence your genetic variations have on your health and body: ➤ Based on your genetic profile, you have a lower than average risk of Alzheimer's Your risk for Alzheimer's disease PROTECTION
AVERAGE RISK
INCREASED
▲ Required antioxidants NORMAL
INCREASED
▲
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METABOLISM
Prevention Your genetic profile shows that you have a lower than normal chance of developing Alzheimer's. However, you can reduce your risk even further by taking measures that reduce the likelihood of developing Alzheimer's. Clinical studies have shown that the following measures reduce the risk of Alzheimer's: Exercise: studies show that regular physical activity reduces the risk of developing Alzheimer's. At least 15 minutes of physical activity 3 days per week can reduce the risk by as much as 40%. It is recommended that you follow a exercise program that you enjoy, and also consider joining an exercise group or gym. Socializing: Studies have found that socially active people have a lower risk of developing dementia. Regular contact with friends or participation in different groups will both benefit you. Therefore, keep in touch with friends and stay active in social groups in your community. Smoking: smoking has many negative health effects and it is always a good idea to quit. Smoking is a risk factor for Alzheimer's, and so if you have a genetic predisposition for Alzheimer’s it is absolutely necessary for you to quit smoking. Diet: diet seems to play an important role in the prevention of Alzheimer's. Since free radicals can cause damage to the brain cells, a diet high in antioxidants is recommended for brain health. Antioxidants include: ➤ Vitamin C: can be found in citrus fruits, kiwi, currants, sea buckthorn, peppers, cabbage and tomatoes. ➤ Vitamin E: a fat-soluble vitamin found in cereals, nuts and various vegetable oils. ➤ Beta-carotene: is contained in various fruits and vegetables such as apricots, peaches, tomatoes, peppers, broccoli, cauliflower, green cabbage, spinach and carrots. ➤ Flavonoids: contained in cherries, plums, berries , apples, red cabbage, red radish, onions , radishes, radicchio and eggplant. ➤ Saponine: in peas, beans, and spinach. ➤ Sulfides: can be found in garlic, shallots, chives, leeks and spring onions. ➤ Polyphenols: in red wine. ➤ Studies have also found that a Mediterranean diet provides some protection against Alzheimer's and other diseases. This type of diet includes large amounts of fruits, vegetables and beans, plenty of fish, a limited amount of dairy products, very little meat and poultry, olive oil, and moderate, but regular, wine.
Education and mental stimulation: studies have shown that a high level of education and frequent mentally challenging activities (including puzzles, reading, listening to the radio, and cultural activities) reduce the likelihood of Alzheimer's by as much as 75% and can also significantly delay its development. Spending long hours in front of the TV seems to increase the chance of developing Alzheimer's. Pick a mentally challenging hobby that mentally challenges you (crossword puzzles, chess, art appreciation, etc.) and practice it regularly. Cholesterol: high cholesterol also contributes to the development of Alzheimer's, and so you should have your cholesterol checked every six months. If your cholesterol is too high, you lower it with Page 105 of 180
exercise and diet. If these are not effective, your doctor may prescribe cholesterol-lowering drugs. A healthy cholesterol level is important for preventing both atherosclerosis and Alzheimer’s. Blood pressure: high blood pressure is one of the most significant risk factors in the development of Alzheimer’s disease. Measure your blood pressure regularly (1 time a week) after 10 minutes of sitting, and try to keep it in the normal range. If your blood pressure is too high, the following measures can lower it. If these steps do not lower your blood pressure into the normal range, talk to your doctor about the possibility of taking medication to lower your blood pressure.
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METABOLISM
Effect on relevant drugs The following genes and polymorphisms reduce the effectiveness of some of the drugs that are routinely used for this disease. Your analysis found the following:
Alzheimer's drugs Drugs for the treatment of Alzheimer's disease
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
donepezil
Normal
~80%
common
~100%
Not neccessary
galantamine (FDA!)
Normal
~0%
common
0%
Advisable
tacrine
Normal
~100%
Normal
~100%
Not neccessary
Drugs for high blood pressure (antihypertensive) Drugs for the treatment of high blood pressure, cardiac insufficiency and cardiac arrhythmia
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
amlodipine
Normal
~100%
Normal
~100%
Not neccessary
atacand
likely higher
~100%
Normal
~100%
Not neccessary
bosentan
Normal
~100%
Normal
~100%
Not neccessary
candesartan
Normal
~100%
Normal
~100%
Not neccessary
diltiazem
Normal
~100%
Normal
~100%
Not neccessary
felodipine
Normal
~100%
Normal
~100%
Not neccessary
irbesartan
Normal
~100%
Normal
~100%
Not neccessary
lercanidipine
Normal
~100%
Normal
~100%
Not neccessary
losartan
likely higher
~100%
Normal
~100%
Not neccessary
nifedipine
Normal
~100%
Normal
~100%
Not neccessary
nisoldipine
Normal
~100%
Normal
~100%
Not neccessary
nitrendipine
Normal
~100%
Normal
~100%
Not neccessary
verapamil
Normal
~100%
Normal
~100%
Not neccessary
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Cholesterol-lowering drugs (Statins) Drugs for lowering cholesterol
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
atorvastatin
Normal
~100%
Normal
~100%
Not neccessary
cerivastatin
Normal
~100%
Normal
~100%
Not neccessary
fluvastatin
Normal
~100%
Normal
~100%
Not neccessary
lescol
Normal
~100%
Normal
~100%
Not neccessary
lovastatin
likely higher
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
Page 108 of 180
SCIENCE
Alzheimer Sensor APOE - apolipoprotein E (E2/E3/E4) APOE (apolipoprotein E) metabolizes triglyceride-rich lipoprotein constituents, and plays a central role in the lipid metabolism. The ApoE gene is present in three common types, which are called allele E2, E3 and E4. The E4 allele is associated with an increased risk of heart disease and Alzheimer. RES
Genotype
POP
X
E2/E2
1%
Protection against Alzheimer's disease (OR: 0.7)
E2/E3
6%
Protection against Alzheimer's disease (OR: 0.7)
E3/E3
66% No increased risk of Alzheimer's disease
E2/E4
2%
E3/E4
24% Increased risk of Alzheimer's disease (OR: 3.2)
E4/E4
1%
Result options
Increased risk of Alzheimer's disease (OR: 2.5)
Increased risk of Alzheimer's disease (OR: 15)
References Farrer et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997 Oct 22-29,278(16):1349-56. Tang et al. The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA. 1998 Mar 11,279(10):751-5.
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Prevention Early diagnosis Treatment
IRON SENSOR Hemochromatosis: easily prevent iron overload • Genetic assessment of iron uptake capacity • Analysis of the three relevant genetic variations • Recognize elevated iron levels before the organs are damaged • Simple measures for the prevention and treatment • Avoid serious health consequences
METABOLISM
Haemochromatosis (iron overload) The hereditary condition hemochromatosis, also called iron storage disease, is among the most common inherited metabolic diseases. It is caused by defects in the genes that are responsible for regulating the absorption of iron from food. These defects impair the function of these genes and lead to excessive absorption of iron, which, over the years, is deposited in the organs such as liver, heart, pancreas, pituitary gland, and the joints, and damages them. In this case, accompanying diseases such as diabetes and liver cancer may appear. Hemochromatosis is an "autosomal recessive" which usually occurs only when a person has inherited a defective iron storage gene from both parents. People with only one defective gene have a somewhat increased risk of disease, but only 5-10% of people with one gene have elevated iron levels. The inherited form of hemochromatosis is very common in the northern European population. One in ten persons has a defective gene and is thus a carrier, while about one in 200 people has two defective genes and has a high risk of developing the iron storage disease. Some symptoms of iron storage disease, for example elevated liver function, are often misdiagnosed, which leads to a wrong treatment and to the worsening of the symptoms. Misdiagnoses are a common problem and, according to experts, 76% of cases are misdiagnosed. If left untreated, this disease can lead to early death, but it can be treated and even prevented by regular blood donations (4-6 times per year) or through phlebotomy therapy. Therefore, it is helpful to detect a genetic predisposition before symptoms appear. It may be possible to avoid symptoms with the help of preventive measures.
Page 111 of 180
METABOLISM
Genes associated with haemochromatosis Haemochromatosis is usually a recessive disease. This means that HFE genes from both parents must carry the same polymorphism in order for the disease to develop. In cases where only one gene exhibits a genetic variation affecting its function, the risk of elevated blood iron levels is present but the risk of developing the disease is very low. Your gene analysis shows the following:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
HFE
rs1799945
H63D
C/G
-
-
-
RISK
HFE
rs1800730
S65C
A/T
-
-
-
RISK
HFE
rs1800562
C282Y
G/G
-
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Here you can see a summary of the influence your genetic variations have on your health: ➤ Your body absorbs a high proportion of the iron in your food ➤ Your have a significantly elevated risk of haemochromatosis Your risk of haemochromatosis NORMAL
INCREASED
▲
Page 112 of 180
METABOLISM
Prevention Both genes carry the trait for haemochromatosis, and so you have a high risk of developing it. It is especially important for you to take preventative measures to reduce your risk for the disease as much as possible. Affected males usually develop the first symptoms between 20 and 40 years of age, while women usually develop symptoms after menopause. Joint pain in the fingers is one of the first signs of haemochromatosis. We encourage you to see a metabolism specialist, and have the iron levels in your blood measured. Transferrin saturation of more than 60% and serum ferritin of over 300μg/l for men and 200 μg/l for women are considered critical values. ➤ If you do not suffer from anemia or iron deficiency, it is a good idea to donate blood frequently, 5-6 times per year. When you donate blood, you reduce the iron content in your body. If you develop symptoms of haemochromatosis your blood will not be usable in for transfusions. ➤ Also have your iron level is measured twice per year, and ask your doctor about how often you should donate blood. If 5-6 donations per year is not a sufficient preemptive measure, your doctor will identify an increase in iron levels through regular inspections, and if necessary, will start a phlebotomy therapy for you. ➤ Avoid alcohol and also multivitamins that contain iron.
Page 113 of 180
SCIENCE
Iron Sensor HFE H63D - Hemochromatosis (rs1799945) The HFE gene encodes the hereditary hemochromatosis-protein. The protein is expressed on the cell membrane, and forms a complex that enables the binding of the principal iron transport protein, transferrin. Several polymorphisms in the HFE gene are associated with the occurrence of hemochromatosis. RES
Genotype
X
POP
Result options
C/C
64% No increased risk of hemochromatosis
C/G
35% Increased risk of hemochromatosis
G/G
1%
Increased risk of hemochromatosis
References Vujić et al. Molecular basis of HFE-hemochromatosis. Front Pharmacol. 2014 Mar 11,5:42. Carelle et al. Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. Am J Hum Genet. Apr 1997, 60(4): 828–832.
HFE S65C - Hemochromatosis (rs1800730) The HFE gene encodes the hereditary hemochromatosis-protein. The protein is expressed on the cell membrane, and forms a complex that enables the binding of the principal iron transport protein, transferrin. Polymorphisms in the HFE gene are associated with the occurrence of hemochromatosis. RES
Genotype A/A
X
POP
Result options
98% No increased risk of hemochromatosis
A/T
1%
Increased risk of hemochromatosis
T/T
1%
Increased risk of hemochromatosis
References Mura et al. HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood. 1999 Apr 15,93(8):2502-5.
HFE C282Y - Hemochromatosis (rs1800562) The HFE gene encodes the hereditary hemochromatosis-protein. The protein is expressed on the cell membrane, and forms a complex that enables the binding of the principal iron transport protein, transferrin. Several polymorphisms in the HFE gene are associated with the occurrence of hemochromatosis. RES
Genotype
POP
Result options
X
G/G
91%
No increased risk of hemochromatosis
G/A
8%
Increased risk of hemochromatosis
A/A
1%
Increased risk of hemochromatosis
References Vujić et al. Molecular basis of HFE-hemochromatosis. Front Pharmacol. 2014 Mar 11,5:42. Carelle et al. Mutation analysis of the HLA-H gene in Italian hemochromatosis patients. Am J Hum Genet. Apr 1997, 60(4): 828–832.
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Prevention Early diagnosis Treatment
BONE HEALTH SENSOR Osteoporosis: Stopping bone density loss and improving treatment • Genetic assessment of innate osteoporosis risk • Analysis of more than 3 relevant genetic variations • Assessment of calcium absorption capacity • Adapted diet and prevention program for osteoporosis • Effectiveness assessment of various therapies (bisphosphate, raloxifene, alendronate, hormones) • Analysis of more than 12 genetic variations, for the effect of more than 18 relevant drugs • Increased treatment success through customization • Medically supervised prevention program
MOBILITY
Osteoporosis Osteoporosis is a disease that affects the bones. It causes bones to lose mass and strength, and makes them more fragile and easier to fracture. Even in normal development, bones become more likely fracture with age. Bones reach maximum strength at about the age of 30, and bone mass decreases moderately after that time. However, some genetic traits lead to reduced bone strength, which increases the risk of osteoporosis and bone fractures, especially of the hips, forearms and vertebra. This risk grows with age. women, mainly because the body no longer produces the bone-protective hormone estrogen. The disease is very common: one in three women over the age of 50 is diagnosed with osteoporosis. As estrogen, the female sex hormone, plays a significant role for women in the formation of bone, women who have had lower estrogen levels throughout their life (e.g. due to a late start of menstruation or premature menopause) are particularly at risk.
Most fractures involve the hips, forearms and vertebrae. In normal development these bones grow throughout childhood and reach maximum strength at about age 30. After that time, bone mass gradually decreases, leading to somewhat more brittle bones. However, some traits in the genes that are responsible for bone formation can cause your bones to become unusually fragile over time. As you age, this leads to increased bone loss and fractures. About 80% of osteoporosis cases occur in post-menopausal
The osteoporosis is a common disease for men over the age of 70. Although women are more often affected by osteoporosis, this disease affects both sexes, and its development is accelerated by certain risk factors such as poor diet and unhealthy lifestyle. Not only calcium, but also numerous other micronutrients (such as minerals, amino acids, and vitamins) are important in maintaining healthy bones. Bones have the capability to store calcium, but these reserves are depleted in the case of nutritional deficiencies, for providing the calcium needed for other important processes in the body. Vitamin D also plays an important role in the absorption of calcium from food. In the case of the elderly, the conversion to the active form of vitamin D is poor; in addition, the vitamin D intake from food is too low. As such the vitamin D deficiency is a largely spread problem, but one that can be easily solved. The incipient phases of the disease are sometimes not associated with any recognizable symptoms, and the diagnosis is made only when Page 116 of 180
the first bone fractures occur. Previous to this point, the bone density is, however, compromised, and the bones may be fractured even in the case of low injuries or low effort, and can occur, for example, when bending or lifting a heavy bag. If the disease is diagnosed at a late stage, treatment is based on preventing falls and increasing bone density as much as possible. This is achieved through a diet rich in calcium and vitamin D, adequate exercise and by use of medication that promotes bone metabolism. The best defense against osteoporosis is, and will remain, prevention. The earlier the disease is diagnosed, the more quickly you can take action to stop bone deterioration. Preventing bone loss is always easier than recovering lost bone. That is exactly what makes this gene test so valuable for preventative health care: you learn what your personal risk of disease is and can often completely prevent the disease from developing and following a prevention program tailored to your individual needs.
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MOBILITY
Genes associated with osteoporosis So far, scientists have identified 4 genes with traits linked to an increased risk of osteoporosis. An analysis of all 4 traits allows us to determine your genetic risk for osteoporosis as well as some other genetic traits linked to this disease. The following genes affect the preservation of bone mass:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
Col1A1
rs1800012
G/T Pos. 1546 (S/s)
G/G
1
RESPOND
-
-
VDR
rs1544410
G/A IVS7 Pos.+283
G/G
0.61
RESPOND
PROTECT.
-
ESR1
rs2234693
-397T>C
C/C
1
RESPOND
PROTECT.
-
LCT
rs4988235
T>C
T/T
-
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
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Summary of effects Some genetic traits reduce your risk of osteoporosis, while others increase risk. Genetic traits that impair calcium uptake also affect bone mass. Here is a summary of the effects that the genetic variations have on your health and body: ➤ Your risk of osteoporosis is not elevated (OR = 1) ➤ Bisphosphate is especially effective for osteoporosis prevention ➤ You have a normal capacity for absorbing calcium Your risk for osteoporosis PROTECTION
AVERAGE RISK
INCREASED
▲
Effectiveness of bisphosphate therapy HIGH
REDUCED
▲ Your capacity to absorb calcium NORMAL
REDUCED
▲
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MOBILITY
Prevention Genetic analysis shows that you do not have an increased risk of osteoporosis and do not need to place a strong emphasis on taking preventive measures necessary other than the general rules of a healthy life style. However, you should avoid medications that are associated with an increased risk of osteoporosis. Everyone loses some bone mass over time. So even though you do not have a genetic predisposition for osteoporosis, you should still take steps to minimize your bone loss. Eat a balanced diet, and make sure that you consume enough dairy products (if you are not lactose intolerant), which are a good source of calcium. Calcium is the raw material necessary for bone regeneration, and it is vital to make sure you are getting enough. ➤ Ensure an adequate uptake of vitamin D. The body produces this vitamin in the presence of sunlight, so you should spend as much time as possible outdoors. Vitamin D is also contained in food products such as fish, and in lower quantities in milk, as well as in some nutritional supplements (fish oils). Depending on your own requirements, you can also take vitamin D as medical treatment. ➤ Sport is, of course, recommended to everybody. Endurance and mild power oriented exercise is recommended to strengthen the bones and muscles.
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MOBILITY
Effect on relevant drugs The effect that various medications will have on you depends on your genetic profile. Genetic variations indicate that the dosage of some drugs should be adjusted. The following recommendations are based on your genetic analysis:
Painkillers (analgesics) Painkillers
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
alfentanil
Normal
~100%
Normal
~100%
Not neccessary
buprenorphine
Normal
~100%
Normal
~100%
Not neccessary
codeine (FDA!)
likely higher
~20%
common
~20%
Advisable
enflurane
Normal
~100%
Normal
~100%
Not neccessary
fentanyl
Normal
~100%
Normal
~100%
Not neccessary
halothane
Normal
~100%
Normal
~100%
Not neccessary
hydrocodone
Normal
~0%
common
0%
Advisable
isoflurane
Normal
~100%
Normal
~100%
Not neccessary
levacetylmethadol
likely higher
~100%
Normal
~100%
Not neccessary
lidocaine
Normal
~100%
Normal
~100%
Not neccessary
methadone
Normal
~90%
Normal
~100%
Not neccessary
methoxyflurane
Normal
~100%
Normal
~100%
Not neccessary
oxycodone
Normal
~0%
common
0%
Advisable
paracetamol
Normal
~100%
Normal
~100%
Not neccessary
phenacetin
Normal
~100%
Normal
~100%
Not neccessary
ropivacaine
Normal
~100%
Normal
~100%
Not neccessary
sevoflurane
Normal
~100%
Normal
~100%
Not neccessary
tramadol (FDA!)
likely higher
~40%
common
~50%
Advisable
zolmitriptan
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
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SCIENCE
Bone Health Sensor Col1A1 - Collagen, type I, alpha 1 (rs1800012) The protein encoded by COL1A1 (collagen type I, alpha 1) is the main protein component of the bone matrix. Defects in the COL1A1 structure cause changes in the bone matrix. RES
Genotype
POP
Result options
X
G/G
81%
No increased risk for osteoporosis BIS-phosphonate therapy is effective
G/T
17%
Increased risk of osteoporosis (OR: 1.26) BIS-phosphonate therapy is less effective
T/T
2%
Increased risk of osteoporosis (OR: 1.78) BIS-phosphonate therapy is less effective
References Jin et al. Polymorphisms in the 5' flank of COL1A1 gene and osteoporosis: meta-analysis of published studies. Osteoporos Int. 2011 Mar,22(3):911-21. Qureshi et al. COLIA1 Sp1 polymorphism predicts response of femoral neck bone density to cyclical etidronate therapy. Calcif Tissue Int. 2002 Mar,70(3):158-63. Epub 2002 Feb 19.
VDR - Vitamin D (1,25- dihydroxyvitamin D3) receptor (rs1544410) The vitamin D receptor protein (VDR) is the primary regulator of calcium and bone metabolism. Vitamin D also controls a variety of important functions, such as: calcium absorption, bone growth and the production of hormones. A defect in this gene leads, inter alia, to changes of the bones density. RES
Genotype
POP
Result options
X
G/G
35% Protection against osteoporosis (OR: 0.61) Hormone replacement therapy is effective in the prevention of osteoporosis Raloxifene is less effective in the treatment of osteoporosis Bisphosphonate therapy is effective
A/G
43% Increased risk of osteoporosis (OR: 1.26) BIS-phosphonate therapy is less effective
A/A
22% Increased risk of osteoporosis (OR: 1.78) BIS-phosphonate therapy is less effective
References Jia et al. Vitamin D receptor BsmI polymorphism and osteoporosis risk: a meta-analysis from 26 studies. Genet Test Mol Biomarkers. 2013 Jan,17(1):30-4. Palomba et al. BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporos Int. 2005 Aug,16(8):943-52. Palomba et al. Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes. Hum Reprod. 2003 Jan,18(1):192-8.
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ESR1 - Estrogen receptor 1 (rs2234693) Estrogens have a positive effect on the human skeleton, through the regulation of bone metabolism, the control of the optimal bone mass and the limitation of bone loss. Defects in this gene can negatively influence these effects. RES
Genotype
POP
Result options
X
C/C
15%
No increased risk for osteoporosis Hormone replacement therapy is effective in the prevention of osteoporosis
C/T
51%
Increased risk of osteoporosis (OR: 2) Hormone replacement therapy is less effective in the prevention of osteoporosis
T/T
34% Increased risk of osteoporosis (OR: 4) Hormone replacement therapy is less effective in the prevention of osteoporosis
References Sonoda et al. Interaction between ESRÎą polymorphisms and environmental factors in osteoporosis. J Orthop Res. 2012 Oct,30(10):1529-34. Wang et al. Susceptibility genes for osteoporotic fracture in postmenopausal Chinese women. J Bone Miner Res. 2012 Dec,27(12):2582-91 van Meurs JB et al. Association of 5' estrogen receptor alpha gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Hum Mol Genet. 2003 Jul 15,12(14):1745-54.
LCT - lactase (rs4988235) The LCT gene provides instructions for making the lactase protein, an enzyme which helps to digest lactose in the small intestine, so that it can be absorbed. If the LCT gene is defective, the lactose cannot be properly digested. In this case the lactose intolerance occurs. Avoiding the dairy products leads to a reduced absorption of calcium. RES
Genotype
POP
Result options
X
T/T
55% Normal calcium intake from food
T/C
36% Normal calcium intake from food
C/C
9%
Reduced calcium intake from food
References Koek et al. The T-13910C polymorphism in the lactase phlorizin hydrolase gene is associated with differences in serum calcium levels and calcium intake.
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Prevention Early diagnosis Treatment
JOINT SENSOR Rheumatoid arthritis: prevention and efficiency treatment of inflammatory joint diseases • Genetic assessment of your disease risk • Analysis of the two relevant genetic variations for arthritis and intervertebral disc disease • Genetically customized nutrition and prevention program • Micronutrient recommendations for prevention and treatment • Analysis of over 18 genetic variations, for the effect of more than 34 relevant drugs • Increased treatment success by customizing the therapy • Medically supervised prevention program
MOBILITY
Inflammatory joint diseases An incorrectly programmed immune system can cause a number of joint diseases. Sometimes our immune system falsely identifies parts of joints as bacterial infections and attacks them by sending immune system cells into the joints where they cause inflammation. This process can lead to conditions such as arthritis or ankylosing spondylitis (AS), which in advanced stages causes the spine to fuse. This severe disease is estimated to affect 1.6 million people in Germany alone, many of whom are unaware of their condition because the initial symptoms are mild. Onset of rheumatoid arthritis can take place at an early age. The immune system of affected individuals attacks and destroys joint cartilage due to a (often genetically determined) programming error. In severe cases, the cartilage may be destroyed completely, causing the bones of the joint to rub against one another. This rubbing shortens the bones of the joint, causing them to slowly stop functioning. Patients mobility is increasingly impaired, their joints deform and fuse together. In severe cases, patients can expect increasing disablement and eventual invalidity. Rheumatoid arthritis cannot be cured, but the earlier it is diagnosed and treated, the better its progress can be delayed.
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MOBILITY
Genes associated with joint diseases The scientific community has linked several genes and polymorphisms to a risk of various cardiovascular diseases. An analysis of these polymorphisms allows us to determine your genetic risk for these diseases as well as some other genetic traits linked to this disease.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
TNF-α
rs1800629
A>G
G/G
1
-
-
-
IL1A
rs1800587
C>T
C/C
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Here you can see a summary of the influence your genetic variations have on your health and body: ➤ Your risk of rheumatoid arthritis is lower than average ➤ You do not have an elevated risk of degenerative disc disease Your risk of rheumatoid arthritis NORMAL
INCREASED
▲
Your risk of degenerative disc disease NORMAL
INCREASED
▲
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MOBILITY
Prevention You have no genetic predisposition for developing joint diseases such as arthritis or disc degeneration. You do not need to take special precautions or prevention programs because your risk is average. If you have joint problems, talk with your doctor to diagnose the cause of your symptoms and determine the proper treatment.
The current treatment methods are effective for the majority of patients if the joint disease is detected early enough. Symptoms such as inflammation and pain can be controlled if detected early. However, the commitment of the patient is crucial for the success of the treatment
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MOBILITY
Effect on relevant drugs Your genetic profile has the following effects on drugs that are used for joint diseases. This information indicates POSSIBLE side effects. Do not make any changes to your medications without the advice and knowledge of your primary care physician.
Anti-inflammatory drugs (anti-rheumatic) Drugs for the treatment of joint diseases
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
aceclofenac
Normal
~100%
Normal
~100%
Not neccessary
budesonide
Normal
~100%
Normal
~100%
Not neccessary
celecoxib
Normal
~100%
Normal
~100%
Not neccessary
dexamethasone
Normal
~100%
Normal
~100%
Not neccessary
diclofenac
Normal
~100%
Normal
~100%
Not neccessary
flurbiprofen
Normal
~100%
Normal
~100%
Not neccessary
hydrocortisone
Normal
~100%
Normal
~100%
Not neccessary
ibuprofen
Normal
~100%
Normal
~100%
Not neccessary
indomethacin
Normal
~100%
Normal
~100%
Not neccessary
lornoxicam
Normal
~100%
Normal
~100%
Not neccessary
meloxicam
Normal
~100%
Normal
~100%
Not neccessary
naproxen
Normal
~100%
Normal
~100%
Not neccessary
piroxicam
Normal
~100%
Normal
~100%
Not neccessary
sulfasalazine
Normal
~100%
Normal
~100%
Not neccessary
suprofen
Normal
~100%
Normal
~100%
Not neccessary
tenoxicam
Normal
~100%
Normal
~100%
Not neccessary
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Painkillers (analgesics) Painkillers
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
alfentanil
Normal
~100%
Normal
~100%
Not neccessary
buprenorphine
Normal
~100%
Normal
~100%
Not neccessary
codeine (FDA!)
likely higher
~20%
common
~20%
Advisable
enflurane
Normal
~100%
Normal
~100%
Not neccessary
fentanyl
Normal
~100%
Normal
~100%
Not neccessary
halothane
Normal
~100%
Normal
~100%
Not neccessary
hydrocodone
Normal
~0%
common
0%
Advisable
isoflurane
Normal
~100%
Normal
~100%
Not neccessary
levacetylmethadol
likely higher
~100%
Normal
~100%
Not neccessary
lidocaine
Normal
~100%
Normal
~100%
Not neccessary
methadone
Normal
~90%
Normal
~100%
Not neccessary
methoxyflurane
Normal
~100%
Normal
~100%
Not neccessary
oxycodone
Normal
~0%
common
0%
Advisable
paracetamol
Normal
~100%
Normal
~100%
Not neccessary
phenacetin
Normal
~100%
Normal
~100%
Not neccessary
ropivacaine
Normal
~100%
Normal
~100%
Not neccessary
sevoflurane
Normal
~100%
Normal
~100%
Not neccessary
tramadol (FDA!)
likely higher
~40%
common
~50%
Advisable
zolmitriptan
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
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SCIENCE
Joint Sensor TNF-α - tumor necrosis factor a (TNF superfamily, member 2) (rs1800629) The tumor necrosis factor (TNF or TNF-α) is a cytokine of the human immune system, regulating the activity of the immune cells. TNF regulates apoptosis, cell proliferation, cell differentiation and the secretion of various cytokines. The polymorphism rs1800629 leads to a highly increased TNFa expression, and thus to an increased inflammatory capacity. RES
Genotype
X
G/G
67% No increased risk of rheumatoid arthritis
POP
Result options
G/A
31%
Increased risk for rheumatoid arthritis (OR: 2.9)
A/A
2%
Increased risk for rheumatoid arthritis (OR: 7.29)
References Dayer et al. The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology 2003,42(Suppl. 2):ii3–ii10 Goldring et al. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 2003,42(Suppl. 2):ii11–ii16 Oregón-Romero et al. Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Association with messenger RNA expression and sTNFalpha. J Investig Med. 2008 Oct,56(7):937-43.
IL1A - interleukin 6 (rs1800587) The interleukin-1 gene cluster on chromosome 2 contains the genes for IL1A and IL1B. In the presence of these polymorphisms (rs1800587 and rs1143634), the T allele increases the IL-1 synthesis, leading to an increase of the inflammatory capacity. RES
Genotype
POP
T/T
7%
X
Result options Increased risk of rheumatoid arthritis (OR 1.36) Increased risk of degenerative disc disease (OR: 7.87)
T/C
36% Increased risk of rheumatoid arthritis (OR 1.17) Increased risk of degenerative disc disease (OR: 1.31)
C/C
57% No increased risk of rheumatoid arthritis
References Virtanen et al. Occupational and genetic risk factors associated with intervertebral disc disease. Spine (Phila Pa 1976). 2007 May 1,32(10):1129-34. Dayer et al. The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Rheumatology 2003,42(Suppl. 2):ii3–ii10 Goldring et al. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 2003,42(Suppl. 2):ii11–ii16
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Prevention Early diagnosis Treatment
GLUTEN SENSOR Early detection and nutrition adjustments • Classification as a "risk group" or "no-risk group" • Immediate detection of symptoms • Analysis of the HLA DQ 2.5 and DQ 8 gene variations, that influence the risk of disease • Adjusting the diet for complete freedom from symptoms • Protection against sometimes fatal sequels • Medically supervised action program
DIGESTION
Gluten intolerance Gluten intolerance, also known as celiac disease, is a widespread food intolerance that affects approximately 1 in 120 Europeans. While a person can develop gluten intolerance at any age, it is especially prevalent in two stages of life: when an infant is introduced to solid food, or between 30 and 40 years of age. Women are affected more frequently than men. Gluten is a protein found in many foods. In some people, gluten triggers an immune response in the intestine that attempts to fight gluten as if it were a bacterial infection. 95% of gluten intolerance cases are caused by a hereditary trait in two specific genes that are involved in regulating the immune system. The body's response to gluten usually leads to a chronic condition causes damage to the small intestine and a variety of other symptoms including diarrhea, loss of appetite and weight loss. If untreated, it can eventually cause malnutrition, fatigue, and occasional vomiting. For infants and toddlers, these can cause growth disorders. Because the symptoms of gluten intolerance are so varied, it is difficult to diagnose and can go unrecognized for many years. At the same time, some people believe that they are intolerant to gluten when they are actually suffering from other conditions. A genetic test will help you and your doctor understand whether you are gluten-intolerant. Gluten intolerance is often accompanied by other conditions, including type 1 diabetes, anemia, and osteoporosis. Other conditions, such as lactose intolerance, can develop. If a gluten-intolerant person continues to consume gluten over a period of years, it can cause serious damage to the intestine. In the worst case, untreated gluten intolerance can cause tumors in different parts of the body. The mortality rate for untreated gluten intolerance is 12%. This risk can generally be eliminated with proper treatment and adjustment to the diet. Damage to intestinal villi prevents the body from absorbing essential nutrients, which can result in vitamin and mineral deficiency. For this
reason, it is important that affected individuals adhere to a balanced, gluten-free diet and take necessary dietary supplements. There is currently no cure for gluten intolerance, and the treatment consists of a lifelong glutenfree diet. Proper treatment usually leads to the regeneration of the intestinal mucosa and the complete disappearance of symptoms. Affected individuals must familiarize themselves with the list of foods containing gluten, and also check ingredient lists on food packaging. In rare cases, when the affected person does not respond well to the diet, other medical treatment is possible. Even though gluten intolerance is fairly common, it is often misdiagnosed as a common digestive disorder because its symptoms are so variable. This gene test is a valuable tool for helping you to determine your risk for gluten intolerance. If you have elevated risk, you can adjust your diet accordingly to avoid further discomfort and prevent particularly harmful secondary conditions.
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DIGESTION
The genetics of gluten intolerance The development of gluten intolerance is largely dependent on the presence of certain polymorphisms. The analysis of these polymorphisms shows the following:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
HLA DQ2.5
rs2187668
HLA DQ2.5
G/G
-
-
PROTECT.
-
HLA DQ8
rs7454108
HLA DQ8
T/T
-
-
PROTECT.
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Gluten intolerance only occurs in people who have specific genes. People who do not have the genetic trait associated with gluten intolerance have virtually no risk of developing it. However, many people with the gluten intolerance gene never actually develop the disease. Even if you are at risk for gluten intolerance, there is a good chance that you will never actually develop it. However, you should pay close attention to your body so you can recognize symptoms early and prevent damage by adopting the right diet. Here you can see a summary of the influence your genetic variations have on your health and body: ➤ Your genetic profile does not contain genes associated with gluten intolerance ➤ You do not have an elevated risk of gluten intolerance Risk of gluten intolerance VERY LOW
INCREASED
▲
Page 133 of 180
DIGESTION
Prevention You have an average risk of gluten intolerance. We do not recommend any special precautions or a gluten-free diet. The following areas are only informative. It is very important for people who are gluten-intolerant to follow a balanced diet that completely eliminates gluten-containing foods. A gluten-free diet will reduce and sometimes eliminate symptoms. In addition, a controlled diet can restore the normal condition of the small intestine even if it has already been damaged, which helps you avoid further complications. A diet plan should start by reducing gluten consumption and, if possible, completely eliminating gluten from the diet. Therefore, a person who is intolerant to gluten should become familiar with all potential sources of gluten. The symptoms of gluten intolerance vary widely from person to person, mostly depending on the amount of damage that was already caused to the small intestine. Some people are affected by very low gluten levels and must follow a gluten-free diet for their whole lives. It is especially important for them to be familiar with a detailed list of foods containing gluten. In most cases, symptoms will resolve quickly and not recur once gluten is eliminated from the diet. However, if the diet has no effect then the patient must undergo medical treatment. Is is especially important to seek treatment to ensure that the symptoms are not caused by another disease. Furthermore, when the small intestine is irritated by gluten, it cannot absorb essential nutrients such as vitamins and minerals. A person with gluten intolerance must take additional measures to ensure that his body has enough vitamins and minerals (in the form of a balanced gluten-free diet or through supplements). Gluten intolerance may lead to lactose intolerance, in which case the patient should avoid milk and dairy products as well. By following a gluten-free diet, it is possible that the intestine will recover enough to be able to digest milk and dairy products in the future.If you suspect you suffer from gluten intolerance, you should double check with a doctor. Celiac disease can be diagnosed by examining the colon and performing a blood test for specific antibodies. Speak with your doctor as soon as the first symptoms appear.
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SCIENCE
Gluten Sensor HLA DQ 2.5 (rs2187668) The human leukocyte antigen system (HLA system) is a group of genes that play a central role in the immune system. It has been shown that certain polymorphisms are associated with the celiac disease. RES
Genotype
POP
Result options
X
G/G
84% Gluten intolerance / celiac disease are practically impossible in the absence of other risk variants.
A/G
15%
There is a genetic predisposition for gluten intolerance
A/A
1%
There is a genetic predisposition for gluten intolerance
References Monsuur et al. Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms. PLoS One. 2008 May 28.3(5):e2270. Wolters et al. Genetic background of celiac disease and its clinical implications. Am J Gastroenterol. 2008 Jan,103(1):190-5. Louka et al. A collaborative European search for non-DQA1*05-DQB1*02 celiac disease loci on HLA-DR3 haplotypes: analysis of transmission from homozygous parents. Hum Immunol. 2003 Mar,64(3):350-8.
HLA DQ 8 (rs7454108) The human leukocyte antigen system (HLA system) is a group of genes that play a central role in the immune system. It has been shown that certain polymorphisms are associated with the celiac disease. RES
Genotype
X
T/T
67% Gluten intolerance / celiac disease are practically impossible in the absence of other risk variants.
C/T
30% There is a genetic predisposition for gluten intolerance
C/C
POP
3%
Result options
There is a genetic predisposition for gluten intolerance
References Monsuur et al. Effective Detection of Human Leukocyte Antigen Risk Alleles in Celiac Disease Using Tag Single Nucleotide Polymorphisms. PLoS One. 2008 May 28.3(5):e2270 Wolters et al. Genetic background of celiac disease and its clinical implications. Am J Gastroenterol. 2008 Jan,103(1):190-5. Louka et al. A collaborative European search for non-DQA1*05-DQB1*02 celiac disease loci on HLA-DR3 haplotypes: analysis of transmission from homozygous parents. Hum Immunol. 2003 Mar,64(3):350-8.
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Prevention Early diagnosis Treatment
LACTOSE SENSOR Early detection and nutrition adjustments • Genetic analysis of the innate risk • Analysis of relevant genetic variations • Immediate detection of symptoms • Adjusting the diet for complete freedom from symptoms • Medically supervised action program
DIGESTION
Lactose intolerance Lactose intolerance is the most common food intolerance among the European population: 1 out of 6 Europeans are affected. Before lactose can be absorbed into the bloodstream, it must first be broken down by lactase, an enzyme in the intestine. The intestine produces lactase in childhood, since newborns must be able to digest breast milk in order to survive. As the child's body prepares to digest other foods, the genes responsible for the production of lactase are gradually deactivated. fatigue or skin problems. Most people in the world are lactose intolerant. However, genes that continued to produce lactase through childhood and adulthood spread through populations of ancient people who raised cattle. As a result, most adults from populations with a history of dairy farming have the ability to digest lactose. Today, 5 of of 6 Europeans can enjoy dairy products. Due to this figure, Europeans view lactose tolerance as the norm, whereas persons that cannot digest lactose are considered to suffer from a food intolerance. Thus, we list lactose intolerance as a disease.
As such, even babies who have the ability to digest lactose early on will gradually build up an intolerance to lactose. Eventually, the body is no longer able to digest lactose at all and consumption of lactose can precipitate a broad range of symptoms. Non-digested lactose is an excellent source of nutrients for intestinal bacteria, which seize the opportunity to multiply rapidly in our digestive tract. The lactose is broken down into different acids and fermentation produces various gases. This process results in diverse symptoms that vary in intensity from person to person. Symptoms include digestive problems such as abdominal bloating, cramps and diarrhea as well as a number of nonspecific complaints such as
A lactose-free diet can prevent all symptoms of lactose intolerance. Individuals should familiarize themselves with foods that contain lactose. Unfortunately, lactose intolerance is often misdiagnosed for years as the severity of symptoms depends on the amount of lactose an individual consumes. As symptoms of lactose intolerance are often misinterpreted as general digestive discomfort, gene testing to determine lactose intolerance can help clear up any personal intolerance you may have and prevent further complications.
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DIGESTION
Genes associated with lactose intolerance More than 99% of cases of lactose intolerance are caused by a genetic variation of the gene LCT/MCM6. A person with two copies of this variation will most likely develop lactose intolerance in his or her lifetime. When symptoms will arise and how severe they will be depends on many other factors, including the environment. The analysis of associated polymorphisms shows the following:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
LCT
rs4988235
T>C
T/T
-
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects ➤ You do not have an elevated risk of lactose intolerance ➤ Your daily calcium uptake is average Your risk of lactose intolerance LOW ▲
Your capacity to absorb calcium VERY HIGH
NORMAL
REDUCED
▲
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DIGESTION
Prevention You do not have an increased genetic risk for lactose intolerance. Therefore, you do not have to take any special precautions or follow a lactose-free diet. If you still have problems, provide details to your doctor so you can get a good diagnosis.
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SCIENCE
Lactose Sensor LCT - lactase (rs4988235) The LCT gene provides instructions for making the lactase protein, an enzyme which helps to digest lactose in the small intestine, so that it can be absorbed. If the LCT gene is defective, the lactose cannot be properly digested. In this case the lactose intolerance occurs. Avoiding the dairy products leads to a reduced absorption of calcium. RES
Genotype
X
T/T
55% No increased risk for lactose intolerance Normal calcium intake from food
POP
Result options
C/T
36% No increased risk for lactose intolerance Normal calcium intake from food
C/C
9%
Very high risk for lactose intolerance later in life Reduced calcium intake from food
References Enattah et al. Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002 Feb,30(2):233-7. Rasinperä et al. Transcriptional downregulation of the lactase (LCT) gene during childhood. Gut. Nov 2005, 54(11): 1660–1661.
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Prevention Early diagnosis Treatment
IBD SENSOR Crohn's disease early detection and proper treatment • Assessment of the risk for Crohn's disease • Analysis of the three relevant genetic variations • Immediate detection of the first symptoms • Adapted diet recommendations for symptom
DIGESTION
Crohn's disease The inflammatory gastro-intestinal disease known as Crohn's disease (named after Burill Bernhard Crohn, the first gastroenterologist who identified and described it) is a chronic and progressive intestinal disease that can affect the entire digestive tract. An abnormal immune reaction causes inflammation of the intestine in multiple locations, which causes digestive problems such as diarrhea and cramps. The inflammation mostly occurs in the colon and small intestine, and more rarely the mouth and esophagus. Damage to the intestinal tissue increases if the inflammation persists. Approximately one in 700 Europeans suffer from this inflammatory intestinal disease (Crohn's disease), which can be triggered by an inherited error in the intestine gene 1 (NOD2). This gene is involved in the function of the immune system. Symptoms most often appear for the first time in people between 16 and 35, or people over 60. Crohn's disease is usually intermittent, with periods of remission alternating with intensive manifestation of symptoms. However, in some cases, this disease can also be chronically active. In many cases, it can take years to correctly diagnose the disease because the first symptoms are temporary digestive issues. Left untreated, the disease leads to a variety of conditions which must be properly treated. The cause of the disease is not fully understood. Better understanding of the disease may lead to improved treatments. Currently, the best treatment consists of alleviating symptoms and using immunosuppresants to reduce the immune reaction. Treatment is aimed at reducing the severity of episodes, preventing further attacks, and treating complications such as strictures, fistulas and perforation of the intestinal tissue. In most cases this leads to a significant improvement in the quality of life of those affected. Because many cases are not diagnosed, this genetic test is recommended for people with recurring digestive problems, as it identifies an increased risk of inflammatory bowel disease, and where applicable, the right diagnosis. Page 142 of 180
DIGESTION
Relevant genes for Crohn's disease The analysed genes have an influence on your risk of developing Crohn's disease and ulcerative colitis. At present there is no way to reduce your risk of developing Crohn's disease, but an accurate diagnosis and proper medical care can significantly reduce the discomfort. The main benefit of this genetic analysis is to determine your risk for Crohn's disease. Close attention to the early symptoms of the disease will help your doctor to make an accurate diagnosis relatively quickly and spare you a long ordeal of searching for the correct diagnosis and treatment. These diseases can be successfully treated by an appropriate diet and a genetically tailored drug therapy.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
NOD2
rs2066844
C>T
C/C
1
-
-
-
NOD2
rs2066845
G>C
G/G
1
-
-
-
NOD2
rs2066847
del>C
C/C
15
-
-
RISK
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Here you can see a summary of the impact your genetic variations have on your health and your body: ➤ Your risk of developing Crohn's disease or ulcerative colitis is approximately 15 -times increased Risk for inflammatory bowel disease LOW
VERY HIGH
â–˛
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DIGESTION
Prevention Based on the genetic profile, you have an increased risk for Crohn's disease. These genetic variations show that you have a increased risk, but this does not necessary means that you will suffer from the disease. It is possible that you will never experience any symptoms. For persons with an increased risk, such as yourself, early detection is very important in order to receive medical treatment from the very beginning. Since in many cases it may take years until the diagnosis is made, you should pay attention to the early symptoms, allowing your doctor to make the correct diagnosis from the first signs of the disease.
These may include some of the following, recurring symptoms: ➤ ➤ ➤ ➤ ➤
Abdominal pain is often the first sign of the disease Frequent diarrhea Increased flatulence Occasionally blood in the stool General bad feeling
A variety of nonspecific symptoms may also occur, which vary in severity from person to person. These include: ➤ ➤ ➤ ➤
Inflammation in various parts of the body such as the eyes or skin Irritation of the joints Discomfort at the spine level Liver or bile duct changes
Inflammatory bowel disease usually occurs in episodes of varying intensity and duration, but can also be chronically active. Phases with minor symptoms alternate with periods of complete freedom from symptoms, which makes the correct diagnosis very difficult. Try to observe if you experience these recurring episodes, and inform your doctor in order to investigate the cause of your digestive problems. PLEASE NOTE: Sporadic digestive symptoms can be caused by many digestive problems. If you have these symptoms, it does not mean that you have inflammatory bowel disease. Smoking is a key risk factor that increases the number and severity of relapses of symptoms. In individuals with a genetic predisposition, smoking increases the risk 20- 40 fold. Smoking has many negative effects on health and it is always beneficial to quit. In your case, quitting smoking will reduce your risk of inflammatory bowel disease by approximately 50%. If you develop any of these symptoms, you should tell your doctor about the symptoms and your genetic risk. This will help in achieving an early diagnosis and rapid treatment.
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DIGESTION
Effect on relevant drugs Your genetic profile has an impact on the effect of drugs prescribed for Crohn's and associated diseases. This information can help your doctor choose the correct dosage of the right medications to minimize side effects.
Anti-inflammatory drugs (anti-rheumatic) Drugs for the treatment of IBD
effect
Breakdown
Adverse Reaction
recommended dose*
alternative?
sulfasalazine
Normal
~100%
Normal
~100%
Not neccessary
budesonide
Normal
~100%
Normal
~100%
Not neccessary
Recommended dosage for the doctor: ~ 100% (simply use the normal dosage), ~ 20% (start with a low dosage and if necessary increase it under supervision), 0% (if possible use an alternative drug), 200% (start normally at 100% dosage and if necessary increase up to 200%)
REMEMBER: Only your doctor can prescribe the correct drugs and dosage. NEVER stop taking a drug or change the dose: consult your doctor instead!
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SCIENCE
IBD Sensor NOD2 - nucleotide-binding oligomerization domain containing 2 (rs2066844) NOD2 (nucleotide-binding oligomerization domain-containing protein 2) is a receptor protein which recognizes bacterial molecules and activates the NF-KB signaling pathway. This is part of the immune response. NOD2 was identified as a Crohn disease associated gene. RES
Genotype
POP
T/T
1%
Increased risk of Crohn's disease (OR: 2.52)
T/C
4%
Increased risk of Crohn's disease (OR: 1.59)
C/C
95% No increased risk of Crohn's disease
X
Result options
NOD2 - nucleotide-binding oligomerization domain containing 2 (rs2066845) RES
Genotype
X
G/G
POP
Result options
98% No increased risk of Crohn's disease
G/C
1%
Increased risk of Crohn's disease (OR: 1.98)
C/C
1%
Increased risk of Crohn's disease (OR: 3.92)
NOD2 - nucleotide-binding oligomerization domain containing 2 (rs2066847) RES
Genotype
POP
X
C/C
1%
Increased risk of Crohn's disease (OR: 15)
del/C
1%
Increased risk of Crohn's disease (OR: 11)
del/del
Result options
98% No increased risk of Crohn's disease
References Jung et al. Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms. PLoS One. 2012,7(12):e52223. Hugot et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001 May 31,411(6837):599-603. Glas et al. The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants. PLoS One. 2010 Dec 30,5(12):e14466. Yazdanyar et al. Penetrance of NOD2/CARD15 genetic variants in the general population. CMAJ. 2010 Apr 20,182(7):661-5.
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Prevention Early diagnosis Treatment
GLAUCOMA SENSOR Detect glaucoma at an early stage and treat it properly • Genetic assessment of innate glaucoma risk • Important information for early detection • Analysis of disease-causing genetic variation • Simple and effective treatment with early diagnosis • Increased protection against one of the leading causes of blindness
OPHTHALMOLOGY
Glaucoma Glaucoma, also called glaucoma, is a common eye disease, and it is one of the leading causes of blindness worldwide. It is estimated that there are currently 500,000 people in Germany suffering from this disease, with many unaware. Approximately 10% of them are blind. Although the disease is easily and effectively treatable with eye drops, most people are unaware of their disease because the symptoms develop slowly, and are noticeable only in the advance phases of the disease. Most cases remain untreated for a long time, leading to optic nerve damage and, in severe cases, to blindness.
further death of nerve cells. Damaged nerve cells cannot be restored. Preventive genetic testing for glaucoma is recommended because it determines your personal risk for glaucoma. If required, start a medical monitoring program, which ensures that the first signs of the disease are immediately recognized and treated properly.
A continuous flow of clear liquid takes place inside the human eye. This is produced in the rear end of the eyeball, and flows to the front parts through the valves. The regulation between the production and outflow creates the pressure in the eye, which is important for the eyes’ shape and function. A gene that which plays an important role in the function of the vent valves was identified some time ago. Unfavorable genetic variations may interfere with the function of the valves so that the produced fluid cannot be properly drained. This leads to a gradual increase in the pressure on the blood vessels that supply the optic nerve with oxygen and nutrients, thus obstructing the blood flow. If this condition persists, the nerves of the eyes start gradually to wither at the far field of vision; in the worst cases it may lead to blindness. The brain combines the image of both eyes, and thus initially compensates for the vision impairment. The disease is usually diagnosed only when both eyes are affected, and the patient experienced difficulties; for example, overlooking parts of the words when reading, or having problems while driving. By this time, the optic nerves are often severely damaged, resulting in most cases in a permanent impairment of the visual field or leading to blindness. After diagnosis, treatment focuses on reducing the eye pressure and on preventing Page 148 of 180
OPHTHALMOLOGY
Relevant genes for glaucoma Science identifies a gene that has an influence on the operation of the drain valves in the eye. As the disease barely manifests itself, and the first vision abnormalities occur only after approximately 95% of the visual cells have died, it is particularly important to detect the disease as early as possible. The main benefit of this genetic analysis is therefore the recognition of one's own risk, leading to earlier and more accurate eye tests; this will allow for an early diagnosis and proper treatment.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
LOXL1
rs3825942
T>C
T/T
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects Here you can see a summary of the impact your genetic variations have on your health and your body: ➤ The risk for glaucoma/open-angle glaucoma is not increased. ➤ Normal eye exams are sufficient for you. Risk for glaucoma NORMAL
INCREASED
▲
Page 149 of 180
OPHTHALMOLOGY
Prevention Based on your genetic profile, you have no increased risk of glaucoma. Therefore, you do not have to take any special precautions, since your risk the same as for the general population. If you experience symptoms, it would still be advisable to discuss this with your doctor, who can diagnose the cause. Since, in rare cases, people with no genetic defect may develop glaucoma, you should undergo a medical eye examination every 2-3 years, starting at age 40. This will help to make an early diagnosis of glaucoma or any other eye disease, and it will allow prompt treatment.
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SCIENCE
Glaucoma Sensor LOXL1 - lysyl oxidase-like 1 (rs3825942) Lysyl oxidase-like 1 (LOXL1) is a copper-dependent protein that plays an important role in elastogenesis. A genetic defect in LOXL1 gene is associated with an increased risk of glaucoma. RES
Genotype
X
POP
Result options
C/C
73% Increased risk of open-angle glaucoma (OR: 40)
C/T
25% Increased risk of open-angle glaucoma (OR: 20)
T/T
2%
No increased risk of open-angle glaucoma
References Thorleifsson et al. Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma. Science. 2007 Sep 7,317(5843):1397-400. Epub 2007 Aug 9.
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Prevention Early diagnosis Treatment
AMD SENSOR Macular Degeneration: effective prevention and early detection for best eye health • Genetic analysis of macular degeneration risk • Analysis of the three relevant genetic variations • Genetically tailored prevention program • Self-test for the early detection • Adapted diet for prevention • Micronutrient recommendation for prevention • Medically supervised action program
OPHTHALMOLOGY
Macular degeneration Macular degeneration is a painless condition affecting the retina of the human eye. The condition usually begins to slowly affect individuals over 50 years of age and impairs the center of the visual field. The condition results in a disruptive spot in the center of the visual field, which can make reading and recognizing details (such as faces) difficult or even impossible without impairing peripheral vision. Macular degeneration is the most common cause of blindness in industrialized countries and roughly 30 million people worldwide are estimated to suffer from the condition. Men and women are equally affected. The layer of tissue sensitive to light in the human eye is known as the retina. The region of the retina where light is most heavily focused is called the macula. This is the point where your vision is at its highest resolution. Macular degeneration occurs when cells in the macula die with increasing age. It may also be aggravated by the formation of new blood vessels or by metabolic waste products that impair macular function. Certain environmental risk factors may accelerate these processes considerably and it is therefore advisable to minimize the effects of such risks as much as possible. These include smoking, heart disease and circulatory system conditions, high blood pressure, a poor diet and extreme exposure to light. Preventative measures focus mainly on minimizing such risk factors in order to delay or prevent development of the condition.
vision, increased difficulty reading, impaired contrast sensitivity and difficulty discerning colors, and increased sensitivity to glare. In advanced stages, the center of the visual field is often only populated by gray shadows which themselves disappear as the condition worsens even further. As the condition affects only the macula, only the center of the visual field is affected. Macular degeneration does not cause total blindness because peripheral vision as well as color vision remain unaffected. Affected individuals thus retain mobility and orientation. Treatment options for advanced macular degeneration are limited and can usually only slow and not reverse the worsening of symptoms. For this reason, prevention and early detection of macular degeneration are of especial importance to facilitate timely treatment of the condition.
Macular degeneration advances slowly over a long period during which symptoms are initially barely noticeable but worsen gradually. Individuals affected usually first experience difficulty reading. Some letters just seem to disappear. Straight lines and edges like window frames appear wavy. This effect can be easily detected and measured by use of a simple test. This is followed by a gradual loss in sharpness of Page 153 of 180
OPHTHALMOLOGY
Genes associated with macular degeneration So far, the scientific community has identified 3 genes and polymorphisms linked to an increased risk of macular degeneration. By analysing all 3 polymorphisms, we are able to determine the resulting disease risk. The following genes affect the development of macular degeneration.
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
HTRA1
rs11200638
G>A
G/G
1
-
-
-
CFH
rs1061170
Y402H, T>C
T/T
1
-
-
-
LOC387715
rs10490924
G>T
G/G
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
Summary of effects ➤ You do not have an elevated risk of macular degeneration ➤ Your requirement of antioxidants is average for your symptoms Your risk of macular degeneration NORMAL ▲
Required antioxidants INCREASED
NORMAL
INCREASED
▲
Page 154 of 180
OPHTHALMOLOGY
Prevention You do not have a genetic predisposition for macular degeneration. You do not need to take special preventive or observation measures because your risk is approximately equal to that of the general population. However, you can still develop macular degeneration, and if you notice symptoms you should discuss them with your doctor. Even people who have no genetic risk can develop macular degeneration. Therefore, you should have an annual eye test after age 40 to allow for early detection and early treatment of the disease. ➤ High blood pressure is a risk factor for macular degeneration. Make sure your blood pressure is within the normal range. You can lower your blood pressure by getting more exercise and adopting the right diet. If diet and exercise do not lower your blood pressure, talk with your doctor about using medication to reduce it. ➤ Smoking is a major risk factor in the development of macular degeneration, and should be avoided. ➤ Protect your eyes from direct sunlight by wearing UV-protective sunglasses or a hat. ➤ Make sure that your diet includes sufficient amounts of antioxidants, such as vitamins. These are contained by fruit and vegetables, and are also available in concentrated form as dietary supplements.
The following sources are recommended: ➤ ➤ ➤ ➤
Antioxidants such as vitamin E, for example from vegetable oil. Vitamin C from peppers and citrus fruits. Carotenoids from green vegetables such as spinach and green cabbage. Food supplement with a combination of vitamins E (α-Tocopherol), C, beta carotene, zinc and copper.
Because the macular degeneration is slow to develop and painless, and requires particular attention to certain symptoms, its early detection plays an important role in determining the best treatment. The symptoms include, among others, shadow or distorted vision (for example, window frames are perceived as wavy), or difficulty in reading (for example, when individual letters disappear). The Amsler grid test will allow you to identify the first signs of distortion in your field of vision. The test can be found on the next page, together with instructions on how to take it. If you notice any symptoms, consult your eye doctor immediately.
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Instructions for macular degeneration self-examination ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤
Hold the Amsler grid at a comfortable reading distance. Cover one eye (if you have reading glasses, please put them on). Fix with the other eye exactly the point in the middle. Look for wavy or blurred lines. This may indicate symptoms of age-related macular degeneration. Repeat the test with the other eye! If the you see the irregularities described, contact your optometrist immediately. Repeat this self-test once a week.
You do not have a genetic predisposition for macular degeneration. You do not need to take special preventive or observation measures because your risk is approximately equal to that of the general population. However, you can still develop macular degeneration, and if you notice symptoms you should discuss them with your doctor.
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SCIENCE
AMD Sensor HTRA1 - HtrA serine peptidase 1 (rs11200638) The polymorphism rs11200638 in the HTRA1 gene (high temperature requirement protein A1) is associated with an increased risk for agerelated macular degeneration. The encoded protein, a serine protease, plays an important role in the quality control of the extracellular matrix proteins. The mutation in the promoter region of the gene leads to the overexpression of the pigment epithelium and to an increased risk of disease. RES
Genotype
POP
A/A
8%
Increased risk of macular degeneration (OR: 8.6)
A/G
41%
Increased risk of macular degeneration (OR: 2.2)
G/G
51%
No increased risk for macular degeneration
X
Result options
References Yang et al. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006 Nov 10,314(5801):992-3. Chen et al. Meta-analysis of the association of the HTRA1 polymorphisms with the risk of age-related macular degeneration. Exp Eye Res. 2009 Sep,89(3):292-300. Dewan et al. HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006 Nov 10,314(5801):989-92.
LOC387715 - Age-related maculopathy susceptibility 2 (rs10490924) The LOC387715 gene locus is located on chromosome 10. The rs10490924 polymorphism is associated with an increased risk of developing age-related macular degeneration. RES
Genotype
POP
X
G/G
61%
G/T
38% Increased risk of macular degeneration (OR: 2.69)
T/T
1%
Result options No increased risk for macular degeneration
Increased risk of macular degeneration (OR: 8.21)
References Fritsche et al. Age-related macular degeneration is associated with an unstable ARMS2 (LOC387715) mRNA. Nat Genet. 2008 Jul,40(7):892-6. Rivera et al. Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet. 2005 Nov 1, 14(21):3227-36. Ross et al. The LOC387715 and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci. 2007,48:1128–1132.
CFH - Complement factor H (rs1061170) A defect in the CFH (complement factor H) gene is regarded, in different studies, as the primary risk for the development of AMD. The complement factor H controls the immune response against various pathogens. RES
Genotype
POP
Result options
X
T/T
15%
T/C
50% Increased risk of macular degeneration (OR: 4)
C/C
35% Increased risk of macular degeneration (OR: 12)
No increased risk for macular degeneration
References Klein et al. Complement Factor H Polymorphism in Age-Related Macular Degeneration. Science. Apr 15, 2005, 308(5720): 385–389. Haines et al. Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005 Apr 15,308(5720):419-21.
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PERIODONTITIS SENSOR Prevent periodontal disease and select the proper implant type • Analysis of 5 relevant genetic variations • Assess the risk for periodontal disease • Adjusted screening program with your dentist • Determine the probability of a titanium implant failure • Potential change to more sustainable materials • Long-lasting dental health
Prevention Early diagnosis Treatment
ODONTOLOGY
Periodontitis Inflammatory periodontitis disease affects the gums and the jawbone. periodontitis disease and tooth decay are the two major oral diseases. More than half of the population between age 35 and 44 suffers from tooth decay, and about 20% of the population has severe tooth decay. Most cases result from poor oral hygiene. Tooth decay is caused primarily by consumption of refined sugar, but oral hygiene helps us prevent tooth decay so that more people have their own teeth during the older age. Since the age of the teeth is crucial for the development of periodontitis disease, this disease is becoming more common. 40% of the population older than 65 suffer from a severe form of the disease. Plaque is constantly forming in our mouth from a combination of food particles, elements of saliva, and bacteria. If this plaque is not removed with brushing and dental care, bacteria breaks the sugar contained in food into acids that attack tooth enamel and cause cavities. Over time, additional material accumulates, which makes the condition worse. In addition to destroying tooth enamel, plaque and tartar penetrate the gums, while the immune system is fighting with their inflammation. This causes gingivitis, the persistent inflammation of the gums. Normally, the immune system can prevent bacteria from spreading further. However, in people with weakened immune systems or other complicating factors, the bacteria are able to spread, infecting the part of the jawbone that holds the teeth. In response, the immune system generates enzymes and chemical mediators that fight the bacterial infection but also attack and gradually destroy the tissues. This powerful immune reaction causes the inflammation of the entire bone, which gradually loosens until the tooth falls out. Most often, the whole jaw is affected: because the tooth only begins to come loose very late, the disease is only diagnosed after it has progressed significantly. Periodontitis disease is caused by a combination of many factors, among which poor oral hygiene and certain genetic traits play a crucial role. Since most of the damage is caused by an immune response, genetic traits that make the response too aggressively, which can lead to severe periodontitis. However, the immune
system responds only when bacteria penetrate into the tissue. This means that people carrying these genetic traits need to take special care of their teeth by avoiding several risk factors: ➤ Poor oral hygiene with dental plaque and tartar ➤ Tobacco use, since smoking increases the risk by 4 to 6 times ➤ Infection with periodontal disease from other affected people (especially within the family) ➤ Tooth decay (cavities) ➤ Mouth breathing ➤ Gnashing of teeth ➤ Unbalanced diet ➤ Piercings in the mouth, lips, frenulum or tongue ➤ Diabetes, especially uncontrolled or poorly controlled ➤ Pregnancy, when hormonal changes loosen connective tissue, which makes it easier for bacteria to penetrate into the gums. ➤ Weakened immune system, such as after a chemotherapy, organ transplantation or in the case of HIV disease.
If the disease is detected early, it can usually be treated very effectively. However, the patient must maintain good oral hygiene in order to prevent a recurrence, since people who have suffered periodontal disease are at increased risk of relapse. If it is not diagnosed and treated, periodontal disease usually leads to loss of teeth, which causes aesthetic and functional problems. This genetic analysis will let you know if you have an increased risk, so that you can Page 159 of 180
take preventive measures and get regular dental checkups to prevent the disease.
Page 160 of 180
Titanium implant loss due to genetic variations Titanium is a popular material for dental implants because it causes no allergic reactions and bonds firmly with the surrounding bone within 3-6 months. The success of treatment strongly varies from person to person, so that some people keep an inserted implant up to several decades, while other people are losing the implant after 4 months. The cause of these differences is different inflammatory responses to titanium, triggered by four different genetic polymorphisms. For people with the optimal genetic profile, the implant failure rate is approximately 3%. However, the risk of implant failure can be as high as 60% for some people, depending on the number of unfavorable genetic variations. If you are likely to lose a hip replacement, People with an unfavorable genetic profile, determined by the genetic analysis, have the opportunity to choose the most appropriate implant, and thus to prevent its premature loss.
Page 161 of 180
ODONTOLOGY
Relevant genes for periodontitis Several genetic variations have been identified, which taken individually slightly increase or decrease the risk of periodontitis. Taken together, they have a significant impact on the risk probability. The analysis of relevant genetic variations came to the following conclusion:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
IL1RN
rs419598
C>T
C/C
1
-
-
-
IL6
rs1800795
G>C
G/G
1
-
-
-
IL1A
rs1800587
C>T
C/C
1
-
-
-
IL 1 Beta
rs1143634
C>T
C/C
1
-
-
-
TNFa
rs1800629
G>A
G/G
1
-
-
-
Probability of a titanium implant loss:
Genetic risks and traits SYMBOL
rs NCBI
POLYMORPH.
GENOTYPE
OR
RESPOND
PROTECT.
RISK
IL1RN
rs419598
C>T
C/C
1.3
-
-
RISK
IL1A
rs1800587
C>T
C/C
1
-
-
-
IL 1 Beta
rs1143634
C>T
C/C
1
-
-
-
TNFa
rs1800629
G>A
G/G
1
-
-
-
LEGEND: rsNCBI = description of investigated genetic variation, polymorphism = form of genetic variation, ODDS RATIO = X-times risk of disease triggered by polymorphism, genotype = personal analysis result, RESPONDER = your body is particularly sensitive because of your genetic traits, PROTECTIVE = your genetic traits give you some protection against the disease, RISK = this genetic variation increases your risk of disease.
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Summary of effects Several genes have an effect on the aggressiveness of the immune system. Some of these genes may affect the likelihood that when the jawbone is infected by bacteria, the immune response will be aggressive enough to destroy bone tissue so that the teeth eventually become loose and fall out. Other genes are controlling how the immune system reacts to titanium implants. Because of them, the probability that your body rejects the titanium implants within four weeks can increase significantly. ➤ Increased risk of titanium implant loss (OR:1.3) ➤ Your risk of developing periodontal disease is not increased. Risk for periodontitis NORMAL
INCREASED
▲
Probability of a titanium implant loss NORMAL
INCREASED
▲
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ODONTOLOGY
Prevention Based on your genetic profile, you have no increased risk of developing periodontitis. Therefore, you should follow only the normal rules of dental hygiene. The following points are important for you: ➤ ➤ ➤ ➤ ➤ ➤ ➤
Brush your teeth in the morning, after every meal and especially in the evening Regularly replace your toothbrush Use floss or an interdental brush to clean between your teeth. Clean the dorsum of the tongue Have your teeth cleaned by a dental hygenist every 3 to 6 months. Do not eat sugar more than once a day, and brush thoroughly immediately afterwards Visit the dentist more frequently if you are pregnant, diabetic, or immunodeficient.
Also avoid, if possible, the following risk factors: ➤ Poor or improper oral hygiene with dental plaque and tartar ➤ Tobacco use, since smoking increases the risk 4 to 6-fold; infection with periodontal disease from other affected people (especially within the family) ➤ Dental caries ➤ Mouth breathing ➤ Gnashing of teeth ➤ Unbalanced diet ➤ Piercings in the mouth, lips, frenulum or tongue ➤ Diabetes, especially uncontrolled or when the blood sugar is poorly controlled. ➤ During pregnancy, hormonal changes loosen in the connective tissue, and bacteria can easily penetrate into the gums. ➤ A reduced immune deficiency, such as after a chemo-therapy, after organ transplantation or in the case of HIV disease.
Since you have a genetic variation which increases the aggressiveness of your immune system, you have a above-average chance of rejecting an implant. You need to decide, together with your dentist, if titanium is the appropriate implant material, or whether you should choose alternatives such as ceramic implants, zirconium oxide implants, coated titanium implants or removable dentures or bridges.
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SCIENCE
Periodontitis Sensor IL1RN - interleukin 1 receptor antagonist (rs419598) The interleukin 1 receptor antagonist (IL1RN) is involved in the regulation of immune and inflammatory responses. The rs419598 polymorphism can enhance the inflammatory activity, which leads to an increased risk of periodontitis. In addition, it was shown that carriers of the C allele have an increased risk of titanium implant loss. RES
Genotype
X
POP
Result options
T/T
47% Increased risk of periodontitis (OR: 3.44) No increased risk of titanium implant loss
T/C
47% Increased risk of periodontitis (OR: 3.44) Increased risk of titanium implant loss
C/C
6%
No increased risk for periodontitis Increased risk of titanium implant loss
References Braosi et al. Analysis of IL1 gene polymorphisms and transcript levels in periodontal and chronic kidney disease. Cytokine. 2012 Oct,60(1):76-82. Trevilatto et al. Association of IL1 gene polymorphisms with chronic periodontitis in Brazilians. Arch Oral Biol. 2011 Jan,56(1):54-62. Baradaran-Rahimi et al. Association of interleukin-1 receptor antagonist gene polymorphisms with generalized aggressive periodontitis in an Iranian population. J Periodontol. 2010 Sep,81(9):1342-6. Komatsu et al. Association of interleukin-1 receptor antagonist +2018 gene polymorphism with Japanese chronic periodontitis patients using a novel genotyping method. Int J Immunogenet. 2008 Apr,35(2):165-70. Jacobi-Gresser et al. Genetic and immunological markers predict titanium implant failure: a retrospective study. Int J Oral Maxillofac Surg. 2013 Apr,42(4):537-43.
IL6 - interleukin 6 (rs1800795) Interleukin-6 is one of the pro-inflammatory cytokines and it is an essential part of the immune response to inflammatory processes. The polymorphism rs1800795, located in the promoter region of the gene, alters the expression of the cytokine. Carriers of the C allele produce less IL6. RES
Genotype
POP
Result options
X
G/G
25% No increased risk for periodontitis
G/C
43% No increased risk for periodontitis
C/C
32% Increased risk of periodontitis (OR: 1.89)
References Nibali et al. Association between periodontitis and common variants in the promoter of the interleukin-6 gene. Cytokine. 2009 Jan,45(1):50-4. de Sรก et al. Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses. Int Endod J. 2007 Jul,40(7):563-72. Babel et al. Analysis of tumor necrosis factor-alpha, transforming growth factor-beta, interleukin-10, IL-6, and interferon-gamma gene polymorphisms in patients with chronic periodontitis. J Periodontol. 2006 Dec,77(12):1978-83.
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IL1A - interleukin 6 (rs1800587) The interleukin-1 gene cluster on chromosome 2 contains the genes for IL1A and IL1B. In the presence of these polymorphisms (rs1800587 and rs1143634), the T allele increases the IL-1 synthesis, leading to an increase of the inflammatory capacity. RES
Genotype
X
POP
Result options
T/T
10% Increased risk of periodontitis (OR: 1.73) Increased risk of titanium implant loss
T/C
50% Increased risk of periodontitis (OR: 1.31) Increased risk of titanium implant loss
C/C
40% No increased risk for periodontitis No increased risk of titanium implant loss
References Jacobi-Gresser et al. Genetic and immunological markers predict titanium implant failure: a retrospective study. Int J Oral Maxillofac Surg. 2013 Apr,42(4):537-43. Nikolopoulos et al. Cytokine gene polymorphisms in periodontal disease: a meta analysis of 53 studies including 4178 cases and 4590 controls. J Clin Periodontol 2008
IL1B - interleukin 1 (rs1143634) The interleukin-1 gene cluster on chromosome 2 contains the genes for IL1A and IL1B. In the presence of these polymorphisms (rs1800587 and rs1143634), the T allele increases the IL-1 synthesis, leading to an increase of the inflammatory capacity. RES
Genotype
POP
T/T
5%
Increased risk of periodontitis (OR: 4.89) Increased risk of titanium implant loss
T/C
31%
Increased risk of periodontitis (OR: 2.85) Increased risk of titanium implant loss
C/C
64% No increased risk for periodontitis No increased risk of titanium implant loss
X
Result options
References Gore et al. Interleukin-1beta+3953 allele 2: association with disease status in adult periodontitis. J Clin Periodontol. 1998 Oct,25(10):781-5. Galbraith et al. Polymorphic cytokine genotypes as markers of disease severity in adult periodontitis. J Clin Periodontol. 1999 Nov,26(11):705-9. Jacobi-Gresser et al. Genetic and immunological markers predict titanium implant failure: a retrospective study. Int J Oral Maxillofac Surg. 2013 Apr,42(4):537-43.
TNF-Îą - tumor necrosis factor a (TNF superfamily, member 2) (rs1800629) The tumor necrosis factor (TNF or TNF-Îą) is a cytokine of the human immune system, regulating the activity of the immune cells. TNF regulates apoptosis, cell proliferation, cell differentiation and the secretion of various cytokines. The polymorphism rs1800629 leads to a highly increased TNFa expression, and thus to an increased inflammatory capacity. RES
Genotype
POP
Result options
X
G/G
67% No increased risk of titanium implant loss
G/A
31%
Increased risk of titanium implant loss
A/A
2%
Increased risk of titanium implant loss
References Jacobi-Gresser et al. Genetic and immunological markers predict titanium implant failure: a retrospective study. Int J Oral Maxillofac Surg. 2013 Apr,42(4):537-43.
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CUSTOMER SERVICE
Customer Service Questions or comments about our service? Our customer service team is happy to help with any enquiries, questions or problems. You can contact us in the following ways:
➤ Office: 0046 (0) 31-30 99 111 ➤ info@dna-medic.com Our team is looking forward to your call. Customer satisfaction is our first priority. If you are not fully satisfied with our service, please let us know. We will do our best to help find a satisfactory solution to your problem.
Contact | Impressum DNA MEDIC SCANDINAVIA AB OLOF ASKLUNDS GATA 1 S-421 30 VÄSTRA FRÖLUNDA SWEDEN
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CERTIFICATIONS
Certifications The Novogenia laboratory is one of the most modern and automated laboratories in Europe, and has numerous certifications and quality assurance systems that meet international standards or even exceed them. The various fields of business are certified separately to the highest standards.
Analysis for Lifestlye-purposes
Analysis of medical genetic samples
Certified through analysis in our ISO 15189 certified laboratory
Certified through analysis in an ISO 17025 certified laboratory
Medical interpretation of genetic analyses
Scientific release of analysis results
Certified through analysis in our ISO 15189 certified laboratory
Licensed for medical genetic analyses by the Austrian government
Company and office Certified through ISO 9001
Page 168 of 180
TECHNICAL DETAILS
Technical details Address
Method of analysis
Olof Asklundsgata 1 42130 Västra Frölunda SWEDEN
Automated DNA extraction, HRM analysis (as needed), mass spectrometry and TaqMAN real time PCR
Order number
Detection rate
DEMO_DNAMEDIC
~99%
Date of birth
Sample type
01/01/1985
Cheek swab / saliva sample
Responsible company
Analysis times
DNA MEDIC SCANDINAVIA AB OLOF ASKLUNDS GATA 1 S-421 30 VÄSTRA FRÖLUNDA SWEDEN
Sample received: 01/06/2014 Analysis started: 02/06/2014 Analysis completed: 04/06/2014 Report generated: 04/06/2014
Analyzing laboratory
Version
Novogenia GmbH Saalachstrasse 92 5020 Salzburg AUSTRIA
v225 HOME
Laboratory director Dr. Daniel Wallerstorfer, B.Sc.
Page 169 of 180
REFERENCES All our results and processes are based on current scientific information and comply completely with all legal requirements. Pharmaco Sensor (Drug side effects) ➤ Bertina, R. M.; Koeleman, B. P. C.; Koster, T.; Rosendaal, F. R.; Dirven, R. J.; de Ronde, H.; van der Velden, P. A.; Reitsma, P. H. : Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369: 64-67, 1994. PubMed ID : 8164741 ➤ J.-M.Hahn, Innere Medizin, 5.Auflage, S.321-323 ➤ Ridker, P. M.; Miletich, J. P.; Stampfer, M. J.; Goldhaber, S. Z.; Lindpaintner, K.; Hennekens, C. H. : Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 92: 2800-2802, 1995. PubMed ID : 7586244 ➤ A.Encke, H.K. Bredding, Die venöse Thrombose- Prophylaxe und Therapie, 2000, S.45-49, S.150-158 ➤ Rosendaal FR, Koster T, Vanderroucke, JP, and others. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504-8. ➤ Internist MR Dr.Karl F.Maier, Thrombosen und Venenerkrankungen, 2003, S.37-82 ➤ Bettina Kemkes-Matthes/Oehler, Blutgerinnung und Thrombose, 3.Auflage, 2001, S.69-132 ➤ Lüllmann, Pharmakologie und Toxologie, 16. Auflage, S.178-199, 362-404 ➤ MSD Manual, Handbuch Gesundheit, 2.Auflage ➤ Lancet. 1995 Dec 16;346(8990):1593-6. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Büller HR, Vandenbroucke JP. ➤ Majerus, P. W. : Bad blood by mutation. Nature 369: 14-15, 1994. PubMed ID : 8164730 ➤ Juul, K.; Tybjaerg-Hansen, A.; Schnohr, P.; Nordestgaard, B. G. : Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Ann. Intern. Med. 140: 330-337, 2004. PubMed ID : 14996674 ➤ Braun, A.; Muller, B.; Rosche, A. A. : Population study of the G1691A mutation (R506Q, FV Leiden) in the human factor V gene that is associated with resistance to activated protein C. Hum. Genet. 97: 263-264, 1996. PubMed ID : 8566967 ➤ Gomes, M. P. V., Deitcher, S. R. (2004). Risk of Venous Thromboembolic Disease Associated With Hormonal Contraceptives and Hormone Replacement Therapy: A Clinical Review. Arch Intern Med 164: 1965-1976 ➤ Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects; Kitty W, Arch Intern Med, Vol 160, Jan 10, 2000. ➤ Anderson J.L. et al., 2007; PMID 17989110 ➤ Flockhart D.A. et al., 2008; PMID 18281922 ➤ Herrington D., 2008; www.theheart.org/article/924397.do ➤ The International Warfarin Pharmacogenetics Consortium, 2009; PMID 19228618
HIV Sensor (HIV resistance) ➤ Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau NR, Phair J, Ho DD, Koup RA. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996 Nov;2(11):1240-3. Fellay J, Ge D, Shianna KV, Colombo S, Ledergerber B, Cirulli ET, Urban TJ, Zhang K, Gumbs CE, Smith JP, Castagna A, Cozzi-Lepri A, De Luca A, Easterbrook P, Günthard HF, Mallal S, Mussini C, Dalmau J, Martinez-Picado J, Miro JM, Obel N, Wolinsky SM, Martinson JJ, Detels R, Margolick JB, Jacobson LP, Descombes P, Antonarakis SE, Beckmann JS, O'Brien SJ, Letvin NL, McMichael AJ, Haynes BF, Carrington M, Feng S, Telenti A, Goldstein DB; NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI). Common genetic variation and the control of HIV-1 in humans. PLoS Genet. 2009 Dec;5(12):e1000791. doi: 10.1371/journal.pgen.1000791.
Epub 2009 Dec 24. Hütter G, Blüthgen C, Neumann M, Reinwald M, Nowak D, Klüter H. Coregulation of HIV-1 dependency factors in individuals heterozygous to the CCR5-delta32 deletion. AIDS Res Ther. 2013 Nov 18;10(1):26. doi: 10.1186/1742-6405-10-26. Agrawal L, Jin Q, Altenburg J, Meyer L, Tubiana R, Theodorou I, Alkhatib G. CCR5Delta32 protein expression and stability are critical for resistance to human immunodeficiency virus type 1 in vivo. J Virol. 2007 Aug;81(15):8041-9. Epub 2007 May 23.
Prostate Health Sensor (Prostate Cancer) ➤ S. Lilly Zheng et al. Cumulative Association of Five Genetic Variants with Prostate Cancer, N Engl J Med 2008;358:910-9 ➤ Holick CN, Stanford JL, Kwon EM, Ostrander EA, Nejentsev S, Peters U. Comprehensive association analysis of the vitamin D pathway genes, VDR, CYP27B1, and CYP24A1, in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2007 Oct;16(10):1990-9. ➤ S. Lilly Zheng et al. Association Between Two Unlinked Loci at 8q24 and Prostate Cancer Risk Among European Americans. JNCI Journal of the National Cancer Institute 2007 99(20):1525-1533 ➤ Zhiyong Ma et al, Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population. Int. J. Cancer: 123, 2574–2579 (2008) ➤ H. Nguyen et al.:Normal Human Ejaculatory Duct Anatomy: A Study of Cadaveric and Surgical Specimens In: The Journal of Urology, Volume 155, Issue 5, Pages 1639-1642 ➤ www.krebshilfe.net ➤ Barry MJ, Fowler FJ, O'Leary MP, et al. (November 1992). "The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association". ➤ eMedicine - Transurethral Microwave Thermotherapy of the Prostate (TUMT) : Article by Jonathan Rubenstein ➤ www.urologielehrbuch.de ➤ PreventProstateCancer.info: A Brief Overview of Benign Prostatic Hyperplasia (BPH) ➤ MacDonald R; Wilt TJ; Howe RW (December 2004). "Doxazosin for treating lower urinary tract symptoms compatible with benign prostatic obstruction: a systematic review of efficacy and adverse effects". BJU International 94 (9): 1263–70. ➤ MacDonald R; Wilt TJ (October 2005). "Alfuzosin for treatment of lower urinary tract symptoms compatible with benign prostatic hyperplasia: a systematic review of efficacy and adverse effects". Urology 66 (4): 780–8. ➤ Roehrborn CG (December 2001). "Efficacy and safety of oncedaily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebocontrolled trial". Urology 58 (6): 953–9. ➤ Holmium Laser Enucleation of the Prostate; Results at 6 Years, Gilling PJ, Aho, TF, Frampton CM, et al. Eur Urol 2008 Apr:53(4):744-9 ➤ Bundesministerium für Gesundheit ➤ http://www.bccancer.bc.ca ➤ Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005). "Cancer statistics, 2005". CA Cancer J Clin 55 (1): 10–30. ➤ Miller DC, Hafez KS, Stewart A, Montie JE, Wei JT (September 2003). "Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base". Cancer 98 (6): 1169–78 ➤ Mongiat-Artus P, Peyromaure M, Richaud P, Droz JP, Rainfray M, Jeandel C, Rebillard X, Moreau JL, Davin JL, Salomon L, Soulié M (December 2009). "[Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology]" (in French). Prog. Urol. 19 (11): 810–7
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➤ Picard JC, Golshayan AR, Marshall DT, Opfermann KJ, Keane TE (November 2009). "The multi-disciplinary management of high-risk prostate cancer". Urol. Oncol ➤ Prostatakrebs-Kodierhilfe. Tumorzentrum Freiburg 2007 ➤ UICC: What are the changes between the 6th and 7th editions? ➤ Christian Wittekind, Hans-Joachim Meyer (Hrsg.): TNM: Klassifikation maligner Tumoren. Wiley-VCH Verlag, 7. Auflage 2010 ➤ Ronald J. Zagoria, Glenn A. Tung: Genitourinary Radiology. Mosby, St. Louis 1997 ➤ Poon KS, McVary KT. Curr Urol Rep. 2009 Jul;10(4):279-86. Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia. ➤ C.M. Yablon, M.P. Banner, P. Ramchandani, E.S. Rovner: Complications of prostate cancer treatment: spectrum of imaging findings. Radiographics (2004) 24(Suppl 1):S181-S194 ➤ G. L. Lu-Yao u. a.: Survival following primary androgen deprivation therapy among men with localized prostate cancer. In: JAMA 300, 2008, S. 173–181 ➤ I. F. Tannock u. a.: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. In: NEJM 351, 2004, S. 1502–1512. ➤ C.R. Porter et al.: 25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series. J Urol. (2006) 176(2):569-74 ➤ American Cancer Society ➤ Deutsche Gesellschaft für Urologie ➤ Berkow SE et al.: Diet and survival after prostate cancer diagnosis. Nutr Rev. (2007) 65(9):391-403 ➤ Kolonel LN: Fat, meat, and prostate cancer. Epidemiol Rev (2001) 23(1):72-81 ➤ Michaud et al.: A prospective study on intake of animal products and risk of prostate cancer. Cancer Causes Control. (2001) 12(6):557-67. ➤ Skinner HG, Schwartz GG: Serum calcium and incident and fatal prostate cancer in the National Health and Nutrition Examination Survey. Cancer Epidemiol Biomarkers Prev. (2008) 17: 2302-5 ➤ Sonnenmangel fördert Krebs!, Medical Tribune, 42. Jg., Nr. 23, 8. Juni 2007, S. 21 ➤ Wigle DT, Turner MC, Gomes J, Parent ME (March 2008). "Role of hormonal and other factors in human prostate cancer". Journal of Toxicology and Environmental Health. Part B, Critical Reviews 11 (3-4): 242–59 ➤ Kirsh VA, Peters U, Mayne ST, Subar AF, Chatterjee N, Johnson CC, Hayes RB (August 2007). "Prospective study of fruit and vegetable intake and risk of prostate cancer". J. Natl. Cancer Inst. 99 (15): 1200–9 ➤ Shannon J, Phoutrides E, Palma A, Farris P, Peters L, Forester A, Tillotson CJ, Garzotto M (2009). "Folate intake and prostate cancer risk: a case-control study". Nutr Cancer 61 (5): 617–28 ➤ Herschman JD, Smith DS, Catalona WJ (August 1997). "Effect of ejaculation on serum total and free prostate-specific antigen concentrations". Urology 50 (2): 239–43
Cardiovascular sensor (cardiovascular disease) ➤ Herold, Innere Medizin 2008 ➤ MSD Manual, Handbuch Gesundheit, Goldmann, 2.Auflage ➤ Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen DGFF e.V ➤ Cholesterin, Wozu wir es brauchen und warum es uns krank macht, C.H.Beck, 1999 Dr. Ursel Wahrburg, Dr. Gerd Assmann ➤ Cholesterin, Risiko für Herz und Gefäße, Edita Pospisil, 2008 ➤ NCEP, Nationales Cholesterin-Erziehungsprogramm ➤ Daniel Steinberg (2007). The Cholesterol Wars: The Cholesterol Skeptics vs the Preponderance of Evidence. Boston: Academic Press. ➤ Philips et al. Gene-nutrient interaction and gender may modulate the association between ApoA1 And ApoB gene polymorphisms and metabolic syndrom risk. Atherosclerosis 2011.214(2):408-14 American Heart Association ➤ Olson RE (February 1998). ""Discovery of the lipoproteins, their role in fat transport and their significance as risk factors"". J. Nutr. 128 (2 Suppl): 439S–443S. PMID 9478044 ➤ Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R (December 2007). ""Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths"". Lancet 370 (9602): 1829–39. ➤ National Cholesterol Education Program (NCEP) ➤ Atherosclerosis. 2011 Feb:214(2):397-403. Epub 2010 Nov 16. Strong association of the APOA5-1131T>C gene variant and earlyonset acute myocardial infarction. De Caterina R, Talmud PJ, Merlini PA, Foco L, Pastorino R, Altshuler D, Mauri F, Peyvandi F, Lina D, Kathiresan S, Bernardinelli L, Ardissino D: Gruppo Italiano
Aterosclerosi ➤ Defesche, J. C.. Kastelein, J. J. P. : Molecular epidemiology of familial hypercholesterolaemia. (Letter) Lancet 352: 1643-1644, 1998 ➤ Hobbs et al. 1992 Hum Mut 1:445 ➤ Defesche et al. 1998 FH workshop 1997 ➤ Lombardi et al. 1998 MEDPED 1998 ➤ Redeker et al. 1998 EAS 98 ➤ Schmidt et al. 2000 Atheroscler 148: 431 ➤ Association of APOE genotype with carotid atherosclerosis in men and women, the framingham Heart Study: Roberto Elosua et al. The journal of lipid research 45, 1868-1875, 2004" ➤ Bilguvar K. et al., 2008; PMID 18997786 ➤ Helgadottir A. et al., 2008; PMID 18176561 ➤ Helgadottir A. et al., 2007; PMID 17478679 ➤ Karvanen J. et al., 2009; PMID 18979498 ➤ Samani N.J. et al., 2007; PMID 17634449 ➤ Schunkert H. et al., 2008; PMID 18362232 ➤ Wellcome Trust Case Control Consortium 2007; PMID 17554300 ➤ Aarnoudse A.J. et al., 2007; PMID 17576865 ➤ Arking D.E. et al., 2006; PMID 16648850 ➤ Eijgelsheim M. et al., 2009; PMID 18927126 ➤ Kao W.H. et al., 2009; PMID 19204306 ➤ Lehtinen A.B. et al, 2008; PMID 18235038 ➤ Newton-Cheh C. et al., 2007; PMID 17903306 ➤ Raitakari O.T. et al., 2009; PMID 18785031 ➤ Ashfield-Watt P.A. et al., 2002; PMID 12081832 ➤ Bonaa K.H. et al.; 2006; PMID 16531614 ➤ Khandanpour N. et al., 2009; PMID 19157768 ➤ Lewis S.J. et al., 2005; PMID 16216822 ➤ Lichtenstein A.H., 2009; PMID 18997166 ➤ Lonn E. et al., 2006; PMID 16531613 ➤ McNulty H. et al., 2008; PMID 18412997 ➤ Ruiz J.R. et al., 2007; PMID 17298693 ➤ Wald D.S. et al., 2006; PMID 17124224 ➤ Wang X. et al., 2007; PMID 17544768 ➤ Angotti E. et al., 1994; PMID 8021234 ➤ Juo S.H. et al., 1999; PMID 10215547 ➤ Ordovas J.M. et al., 2002; PMID 11756058 ➤ Ordovas J.M., 2004; PMID 15070444 ➤ Subbiah M.T., 2007; PMID 17240315 ➤ Tuteja R. et al., 1992; PMID 1618307 ➤ Angelopoulos T.J. et al., 2008; PMID 18806463 ➤ Bennet A.M. et al., 2007; PMID 17878422 ➤ Caslake M.J. et al., 2008; PMID 18779276 ➤ Jofre-Monseny L. et al., 2008; PMID 18203129 ➤ Lovegrove J.A. et al., 2008; PMID 18412994 and PMID 18721398 ➤ Masson L.F. et al., 2003; 12716659 ➤ Minihane A.M. et al., 2007; PMID 17466101 ➤ Minihane A.M. et al., 2000; PMID 10938022 ➤ Aberle J. et al., 2005; PMID 15996212 ➤ Aouizerat B.E. et al., 2003; PMID 12671030 ➤ Dorfmeister B. et al., 2007; PMID 17197160 ➤ Evans D. et al., 2003; PMID 12937897 ➤ Grallert H. et al., 2007; PMID 17768309 ➤ Klos K.L. et al., 2005; PMID 15604515 ➤ Lai C.Q. et al., 2007; PMID 17431185 ➤ Lai C.Q. et al., 2006; PMID 16636175 ➤ Maász A. et al., 2007; PMID 17922054 ➤ Szalai C. et al., 2004; PMID 15177130 ➤ Vaessen S.F. et al., 2006; PMID 16769999 ➤ Wang J. et al., 2008; PMID 18779834 ➤ Yamada Y. et al., 2007; PMID 16806226
Thrombo Sensor (Thrombosis) ➤ Bertina, R. M.; Koeleman, B. P. C.; Koster, T.; Rosendaal, F. R.; Dirven, R. J.; de Ronde, H.; van der Velden, P. A.; Reitsma, P. H. : Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369: 64-67, 1994. PubMed ID : 8164741 ➤ J.-M.Hahn, Innere Medizin, 5.Auflage, S.321-323 ➤ Ridker, P. M.; Miletich, J. P.; Stampfer, M. J.; Goldhaber, S. Z.; Lindpaintner, K.; Hennekens, C. H. : Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation 92: 2800-2802, 1995. PubMed ID : 7586244 ➤ A.Encke, H.K. Bredding, Die venöse Thrombose- Prophylaxe und Therapie, 2000, S.45-49, S.150-158 ➤ Rosendaal FR, Koster T, Vanderroucke, JP, and others. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504-8. ➤ Internist MR Dr.Karl F.Maier, Thrombosen und Venenerkrankungen, 2003, S.37-82 ➤ Bettina Kemkes-Matthes/Oehler, Blutgerinnung und Thrombose, 3.Auflage, 2001, S.69-132 ➤ Lüllmann, Pharmakologie und Toxologie, 16. Auflage, S.178-199,
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Iron Sensor (Hemochromatosis) ➤ Allen, K.J., et al., Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med, 2008. 358(3): p. 221-30. ➤ Bradley, L.A., J.E. Haddow, and G.E. Palomaki, Population screening for haemochromatosis: expectations based on a study of relatives of symptomatic probands. J Med Screen, 1996. 3(4): p. 171-7. ➤ Adams PC, R.D., Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-Foster C, Speechley M, Snively BM, Holup JL, Thomson E, Sholinsky P., Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med, 2005(352): p. 1769–78. ➤ CDCP, Centers for Disease Control and Prevention ➤ GeneticHealth.com. ➤ MFMER, Mayo Foundation for Medical Education and Research. ➤ NDDIC, National Digestive Diseases Information Clearinghouse. ➤ NIH, Institutes of Health. ➤ GFHEV-Leitlinien. ➤ Medicoconsult-Datenbank. ➤ Haemochromatose.org. ➤ Burt, M.J., et al., The significance of haemochromatosis gene mutations in the general population: implications for screening. Gut, 1998. 43(6): p. 830-6. ➤ Leberkrankheiten_Informationswebseite. ➤ Niederau C, F.R., Pürschel A, Stremmel W, Häussinger D, Strohmeyer G, Long-term survivalin patients with hereditary hemochromatosis. Gastroenterology 1996(110): p. 1107-1119. ➤ Rochette, J., et al., Multicentric origin of hemochromatosis gene (HFE) mutations. Am J Hum Genet, 1999. 64(4): p. 1056-62. ➤ "Hemochromatosis: Treatments and drugs". Mayo Foundation for Medical Education and Research (MFMER). http://www.mayocli nic.com/health/hemochromatosis/DS00455/DSECTION=7 ➤ Hemochromatosis National Digestive Diseases Information Clearinghouse, National Institutes of Health, U.S. Department of Health and Human Services ➤ "Hemochromatosis: Symptoms". Mayo Foundation for Medical Education and Research (MFMER). http://www.mayoclinic.com/heal th/hemochromatosis/DS00455/DSECTION=2. ➤ Prevalence of the HFE Gene Mutation in the Liver Transplanted and Primary Hemochromatosis Patients in the Southern Iran, M Yavarian et al. IRCMJ 2010; 12(1):22-26 ©Iranian Red Crescent Medical Journal ➤ HFE mutations in heart disease, Terence Dunn et al. Heart and Vessels, Volume 23, Number 5, 348-355.
Bone Health Sensor (Osteoporosis) ➤ Herold, Innere Medizin 2008 ➤ MSD Manual, 2.Auflage ➤ Seeman, E.; Hopper, J. L.; Bach, L. A.; Cooper, M. E.; Parkinson, E.;
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Joint Sensor (Rheumatoid Arthritis)
➤ Zou J, Zhang Y, Thiel A, Rudwaleit M, Shi SL, Radbruch A, Poole R, Braun J, Sieper J.: Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis. in: Rheumatology (Oxford). 2003 Jul;42(7):846-55 ➤ Abul K. Abbas : Diseases of Immunity in Vinay Kumar, Abul K. Abbas, Nelson Fausto : Robbins and Cotran - Pathologic Basis of Disease, 7. Auflage, Philadelphia, 2005, S. 205 ➤ Gerd Herold. Innere Medizin. Köln 2005 ➤ A. McMichael, P. Bowness. HLA-B27: natural function and pathogenic role in spondyloarthritis. Arthritis Res. 2002;4 Suppl 3:S153-8. ➤ J.C. Edwards et al. Jekyll and Hyde: the transformation of HLAB27. Immunol Today. 2000 Jun;21(6):256-60 ➤ Braun J, Bollow M, Remlinger G et al.: Prevalence of Spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis & Rheumatism 1998;41:58–67 ➤ Porter, Robert; Beers, Mark H.; Berkow, Robert (2006). The Merck manual of diagnosis and therapy. Rahway, NJ: Merck Research Laboratories. pp. 290 ➤ DVMB - Deutsche Vereinigung Morbus Bechterew ➤ P. Bowness: HLA B27 in health and disease: a double-edged sword? Rheumatology 2002; 41: pp. 857—868 ➤ Dennis L. Kasper et al: Harrison's Principles of Internal Medicine, 16. Ausgabe 2005. Seite 1995f ➤ H. Spring, A.Pirlet: Morbus Bechterew, Gymnastik und Sport. Georg Thieme Verlag 1995. ➤ Günstige Ernährung bei Morbus Bechterew, Olaf Adam, WMW Wiener Medizinische Wochenschrift Volume 158, Numbers 9-10, 294-297 ➤ P. Schmied und H. Baumberger. Morbus Bechterew – Der entzündliche Wirbelsäulen-Rheumatismus, 3. Auflage Gustav Fischer Verlag Stuttgart 2003 ➤ E Jaakkola, Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis.Ann Rheum Dis 2006;65:775-780 ➤ Biesalski, H. K., et al., Ernährungsmedizin (2004), Thieme Verlag ➤ DGE-Beratungsstandards: Rheumatische Erkrankungen (2001) ➤ Diättherapie bei rheumatischen Erkrankungen«, Empfehlungen der Deutschen Gesellschaft für Rheumatologie ➤ Osteoarthritis Cartilage. 2006 Mar;14(3):286-94. Epub 2005 Nov
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Gluten Sensor (Celiac Disease) ➤ Innere Medizin, Gerd Herold und Mitarbeiter, 2008 ➤ Curione M, Barbato M, Viola F, Francia P, De Biase L, Cucchiara S. Idiopathic dilated cardiomyopathy associated with coeliac disease: the effect of a gluten-free diet on cardiac performance. Dig Liver Dis. 2002;34:866 –869. ➤ Handbuch Zöliakie, Österreichische Arbeitsgemeinschaft Zöliakie ➤ Farrell R, Kelly C. Celiac sprue. N Engl J Med 2002;346:180–8. ➤ Deutsche Zöliakie Gemeinschaft ➤ Kupper C (2005). "Dietary guidelines and implementation for celiac disease". Gastroenterology 128 (4 Suppl 1): S121–7. ➤ Sblattero D, Berti I, Trevisiol C, et al (May 2000). "Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease". Am. J. Gastroenterol. 95 (5): 1253–7. ➤ Am J Med. 1967; 42: 899-912 ➤ Gut 1989; 30: 333-338 ➤ Hardwick, C. Prognosis in coeliac disease. Arch Dis Child 1939; 14:279. ➤ Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. Monsuur AJ, de Bakker PI, Zhernakova A, Pinto D, Verduijn W, Romanos J, Auricchio R, Lopez A, van Heel DA, Crusius JB, Wijmenga C. PLoS One. 2008 May 28.3(5):e2270.
Lactose Sensor (Lactose Intolerance) ➤ Herold, Innere Medizin 2008, 439-440 ➤ Beja-Pereira, A.; Luikart, G.; England, P. R.; Bradley, D. G.; Jann, O. C.; Bertorelle, G.; Chamberlain, A. T.; Nunes, T. P.; Metodiev, S.; Ferrand, N.; Erhardt, G. : ➤ Gene-culture coevolution between cattle milk protein genes and human lactase genes. Nature Genet. 35: 311-313, 2003. Note: Erratum: Nature Genet. 35: 106 only, 2003. ➤ Laktose-Intoleranz, Thilo Schleip, 5.Auflage, 2003 ➤ Tuula H. Vesa et al.: Lactose Intolerance, in: Journal of the American College of Nutrition, Vol. 19, No. 90002, 165S-175S (2000) ➤ Bulhoes, A. C., et. al. (2007-11). "Correlation between lactose absorption and the C/T-13910 and G/A-22018 mutations of the lactase-phlorizin hydrolase (LCT) gene in adult-type hypolactasia". Brazilian Journal of Medical and Biological Research. ➤ National Digestive Diseases Information Clearinghouse (March 2006). "Lactose Intolerance". National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. ➤ Montalto M, Curigliano V, Santoro L, et al (2006). "Management and treatment of lactose malabsorption". World J. Gastroenterol. 12 (2): 187–91. PMID 16482616. http://www.wjgnet.com/1007-9327/12/187.asp. ➤ Enattah, N. S.; Sahi, T.; Savilahti, E.; Terwilliger, J. D.; Peltonen, L.; Jarvela, I. : Identification of a variant associated with adult-type hypolactasia. Nature Genet. 30: 233-237, 2002. ➤ Olds, L. C.; Sibley, E. : Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum. Molec. Genet. 12: 2333-2340, 2003. ➤ Kuokkanen, M.; Kokkonen, J.; Enattah, N. S.; Ylisaukko-oja, T.; Komu, H.; Varilo, T.; Peltonen, L.; Savilahti, E.; Jarvela, I. : Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency. Am. J. Hum. Genet. 78: 339-344, 2006.
IBD Sensor (Inflammatory Bowel Disease) ➤ Innere Medizin, Herold 2008, S.443-446 ➤ Pimentel, Mark; Michael Chang, Evelyn J. Chow, Siamak Tabibzadeh, Viorelia Kirit-Kiriak, Stephan R. Targan, Henry C. Lin (2000). "Identification of a prodromal period in Crohn's disease but not ulcerative colitis". American Journal of Gastroenterology 95 (12): 3458–62 ➤ Baumgart DC, Sandborn WJ (2007). "Inflammatory bowel disease: clinical aspects and established and evolving therapies.". The Lancet 369 (9573): 1641–57 ➤ J.-M.Hahn, Innere Medizin, 5.Auflage, 378-383 ➤ Hirzel, Chronisch entzündliche Darmerkrankungen, 2.Auflage ➤ MSD Manual, Handbuch Gesundheit, 2.Ausgabe ➤ Tecker, Morbus Crohn und Colitis ulcerosa ➤ Current issues in Crohn's disease, Warwick S. Selby, MJA 2003, 178 (11): 532533 ➤ Ogura, Y.; Bonen, D. K.; Inohara, N.; Nicolae, D. L.; Chen, F. F.; Ramos, R.; Britton, H.; Moran, T.; Karaliuskas, R.; Duerr, R. H.;
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Achkar, J.-P.; Brant, S. R.; Bayless, T. M.; Kirschner, B. S.; Hanauer, S. B.; Nunez, G.; Cho, J. H. : ➤ A frameshift mutation in Nod2 associated with susceptibility to Crohn's disease. Nature 411: 603-606, 2001 ➤ Jacobsen BA et al. Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: a populationbased study, 1978-2002. Eur J Gastroenterol Hepatol. 2006 Jun;18(6):601-6. ➤ Podolsky, Daniel K. (2002). "Inflammatory bowel disease". New England Journal of Medicine 346 (6): 417–29 ➤ Mueller, M. H.; M. E. Kreis, M. L. Gross, H. D. Becker, T. T. Zittel & E. C. Jehle (2002). "Anorectal functional disorders in the absence of anorectal inflammation in patients with Crohn's disease". British Journal of Surgery 89 (8): 1027–31 ➤ Reese GE, Nanidis T, Borysiewicz C, Yamamoto T, Orchard T, Tekkis PP; Int J Colorectal Dis. The effect of smoking after surgery for Crohn's disease: a meta-analysis of observational studies. 2008 Dec;23(12):1213-21. Epub 2008 Sep 2 ➤ King, K.; Sheikh, M. F.; Cuthbert, A. P.; Fisher, S. A.; Onnie, C. M.; Mirza, M. M.; Pattni, R. C.; Sanderson, J.; Forbes, A.; Mansfield, J.; Lewis, C. M.; Roberts, R. G.; Mathew, C. G. : Mutation, selection, and evolution of the Crohn disease susceptibility gene CARD15. Hum. Mutat. 27: 44-54, 2006.
Glaucoma Sensor (Glaucoma) ➤ Augenheilkunde, Grehn, 30.Auflage, Springer ➤ Medikamentöse Augentherapie, Paul U. Fechner ➤ Das MSD Manual der Diagnostik und Therapie, Mark H Beers, MSD Sharp & Dohme GmbH, 7.Auflage ➤ Stone, E. M.; Fingert, J. H.; Alward, W. L. M.; Nguyen, T. D.; Polansky, J. R.; Sunden, S. L. F.; Nishimura, D.; Clark, A. F.; Nystuen, A.; Nichols, B. E.; Mackey, D. A.; Ritch, R.; Kalenak, J. W.; Craven, E. R.; Sheffield, V. C. : ➤ Identification of a gene that causes primary open angle glaucoma. Science 275: 668-670, 1997. ➤ National Insstitute of Health (NIH) - National Eye Institute ➤ J. Flammer: Glaukom. Ein Handbuch für Betroffene. Eine Einführung für Interessierte. Ein Nachschlagewerk für Eilige. Hans Huber Verlag ➤ "Global data on visual impairment in the year 2002" Bulletin of the World Health Organization Volume 82, Number 11, November 2004, 811-890 ➤ Morissette, J.; Cote, G.; Anctil, J.-L.; Plante, M.; Amyot, M.; Heon, E.; Trope, G. E.; Weissenbach, J.; Raymond, V. : A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q. Am. J. Hum. Genet. 56: 1431-1442, 1995. ➤ Kwon, Y. H.; Fingert, J. H.; Kuehn, M. H.; Alward, W. L. M. : Primary open-angle glaucoma. New Eng. J. Med. 360: 1113-1124, 2009. ➤ Rezaie, T.; Child, A.; Hitchings, R.; Brice, G.; Miller, L.; Coca-Prados, M.; Heon, E.; Krupin, T.; Ritch, R.; Kreutzer, D.; Crick, R. P.; Sarfarazi, M. : Adult-onset primary open-angle glaucoma caused by mutations in optineurin. Science 295: 1077-1079, 2002.
AMD Sensor (Macular Degeneration) ➤ Augenheilkunde, Franz Grehn, 30.Auflage, 2008 ➤ MDS Manual, Handbuch Gesundheit, 2.Auflage ➤ Haines, J. L.; Hauser, M. A.; Schmidt, S.; Scott, W. K.; Olson, L. M.; Gallins, P.; Spencer, K. L.; Kwan, S. Y.; Noureddine, M.; Gilbert, J. R.; Schnetz-Boutaud, N.; Agarwal, A.; Postel, E. A.; Pericak-Vance, M. A. : Complement factor H variant increases the risk of age-related macular degeneration. Science 308: 419-421, 2005 ➤ Diagnosen am Augenhintergrund, Thieme, Bernd Kirchhof, Martin Reim, Sebastian Wolf, 2003 ➤ de Jong PT (2006). "Age-related macular degeneration". N Engl J Med. 355 (14): 1474–1485. ➤ Ch. 25, Disorders of the Eye, Jonathan C. Horton, in Harrison's Principles of Internal Medicine, 16th ed. ➤ Richer SP.J Am Optom Assoc. 1993 Dec;64(12):838-50. Is there a prevention and treatment strategy for macular degeneration? ➤ Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, Howes K, Zhang K. "A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration." ➤ Deutsche Ophthalmologische Gesellschaft (DOG) ➤ Klein, R. J.; Zeiss, C.; Chew, E. Y.; Tsai, J.-Y.; Sackler, R. S.; Haynes, C.; Henning, A. K.; SanGiovanni, J. P.; Mane, S. M.; Mayne, S. T.; Bracken, M. B.; Ferris, F. L.; Ott, J.; Barnstable, C.; Hoh, J. : Complement factor H polymorphism in age-related macular degeneration. Science 308: 385-389, 2005 ➤ National Institutes of Health (NIH) - National Eye Institute ➤ Maller, J.; George, S.; Purcell, S.; Fagerness, J.; Altshuler, D.; Daly, M. J.; Seddon, J. M. : Common variation in three genes, including a
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