Liposcan

LABORATORY INFORMATION

LipidGen Optimised analysis of the polymorphisms of genes in the lipid metabolism SPECIAL FEATURE High (LDL) cholesterol levels often cause diet recommendations that not infrequently have no effect or even are counterproductive. The solution of this problem is a differentiated analysis in order to identify the causes of the high cholesterol level.

The determination of the relevant LDL subfractions (e.g. using LipoScan), the sex and in particular the individual genetic components of the lipid metabolism that can be identified by means of LipidGen play a decisive role in estimating the true atherogenic risk and the planning of a special therapy.

LIPIDGEN LipidGen is an optimised composition of gene polymorphisms pertinent to disorders of the lipid metabolism for identifying the essential genetic causes of this disorder. The identified polymorphisms indicate which medication and which diet recommendations are reasonable for the individual case and thus allow pinpoint therapies.

FIELD OF APPLICATION Differential diagnostics for establishing pinpoint therapies in patients with disorders of the lipid metabolism.

CLINICAL BENEFIT r No unnecessary genetic analyses: Only relevant gene polymorphisms are tested the expression of which can be influenced positively by nutrition and lifestyle r Deduction of a special individual therapy for the patient: in case of need, allopathic approaches (lipid-lowering drugs) and/or change in living habits and nutrition r The patient can actively design his lifestyle and its implications r Use in prevention and therapy r Saving of unnecessary drug intake and costs WHICH LIPIDGEN PROFILE IS THE RIGHT ONE? The selection of the right LipidGen profile for the individual case is determined by the results of the LipoScan findings, an InVitaLab medical history sheet on the lipid metabolism and the findings of the metabolic function test on lipid metabolism.

LipidGen profiles

LDLgen / LDLgenplus

HDLgen / HDLgenplus

Field of application

In case of high LDL levels and/ or relative shift towards the atherogenic small LDL particles LDLgen: basic profile LDLgenplus: in case of overweight / diabetes

In case of high HDL cholesterol (with or without high total cholesterol) and without high LDL cholesterol

Importance of nutrition and other environmental influences

Very high

Large influence of nutrition for keeping high HDL levels

Therapeutic effect

Through nutrition adapted to the individual person and change in lifestyle

Particularly suitable for prevention

Special feature

Drugs can be reduced to minimum

Sex-specific approach is required

LipidGen – optimised genetic analysis of the lipid metabolism

Background information WHAT IT IS A GENE POLYMORPHISM? Every human being has the same number (approx.

30,000) and type of genes. Genes are responsible e.g. for the eye colour, the skin colour, the skin type etc., but they also determine how we react to our environment, how our metabolism takes place, even how we build up and degrade fats. Genes can be present in different „forms” (polymorphisms).

This is the basis of our variability and diversity (e.g. the different eye colours: blue, green, brown, and grey).

Most polymorphisms are so-called SNP (single nucleotide polymorphisms). In these cases, a single base of the gene is changed in general. As a consequence, the protein or enzyme coded by this gene may work faster or more slowly or lose its activity completely. Genes are always present in pairs of two (one from the father and one from the mother). If both genes are identical, this is called a homozygous variant, if they are different, this is called a heterozygous variant. In most of the genes, the heterozygous variant does not have a high significance and/or the effect created by it is weaker than that of the homozygous variant.

WHY DOES A SNP ANALYSIS LIKE LIPIDGEN MAKE SENSE IN CASE OF DISORDERS OF THE LIPID METABOLISM? 90% of the disorders of the lipid metabolism are caused by genes that are involved in fat absorption, fat transport, conversion of the lipoproteins and degradation of the fat. Thus, dyslipidaemia can have various genetic causes which again are influenced by environmental influences such as nutrition, alcohol, and smoking or have sex-specific effects as well. This is particularly important for therapy and diet recommendations. Any better or worse effect of drugs can depend on the polymorphism present as well.

Example: In general, Mediterranean nutrition is considered to be good and preventive for coronary cardiovascular diseases (a large quantity of fresh fruit, vegetables and olive oil as well as red wine from time to time which is said to have an antioxidant effect).

Only the examination of the genetic components shows that a certain gene polymorphism beneficial in relation with the Mediterranean nutrition (ApoE2) predominates in the Mediterranean countries. This gene polymorphism is hardly present in the other

countries of Central Europe, on the contrary, 25% of the population have the ApoE4 polymorphism which, in case of Mediterranean nutrition, forms small atherogenic LDL particles, is associated with pro-inflammatory processes and, at the same time, increases the risk of getting Alzheimer’s disease. This means that a quarter of the population thinks to eat healthy when keeping to Mediterranean nutrition – but this may be a very bad nutrition in the individual case on account of the genetic disposition.

Today, not more sweeping recommendations should be made, but they should be adapted to the individual person. This can be achieved by means of LipidGen. THE GENETIC PROFILES COMPRISE THE FOLLOWING GENE POLYMORPHISMS: APOE: ApoE2 results in family hypercholesterolaemia as well as small LDL particles. ApoE4 results in an increased risk of arteriosclerosis and Alzheimer’s disease. Depending on the polymorphism, Mediterranean nutrition may be beneficial or contraindicated.

APOA1: A certain polymorphism determines the influence of unsaturated fatty acids on the increase or decrease of the HDL level in particular in women.

APOA5: Several polymorphisms are associated with high plasma triclyceride levels. Be careful regarding polyunsaturated fatty acids: In case of certain polymorphisms, the patients should only be supplemented using Omega 3 fatty acids.

FABP2: The homozygous variant has a strongly increased affinity for long fatty acids. Persons having this polymorphism should clearly reduce their intake of fat.

PPARγ: This polymorphism gives a statement on whether protein or carbohydrate intake should be preferred.

ADBR: Relevant in case of adiposity. It provides an indication for increased disposition to create fat depots. This can be used to derive nutrition physiological recommendations.

NPY: Among other things, the neuropeptide Y controls the sensation of hunger. Several gene polymorphisms are known that in part result in high LDL levels.

CETP: The different polymorphisms have an influence on the HDL concentration.

LPL: Lipase has three polymorphisms with different pro- and anti-atherogenic properties.

Case study of cardiovascular risk assessment LipidGen Findings

Patient A

Patient B

Cholesterin T+LDL

normal

high

Triglyceride

normal

high

LipoScan

pathological

pathological

APOE

E2/E3

E3/E4

APOA5

mutant C/C

wild type T/T

APO B

wild type

wild type

APOCIII

wild type

wild type

CETP

wild type

wild type

FABP2

wild type A/A

heterozygous A/T

LDL-R

wild type A/A

wild type A/A

Therapie

Patient A

Patient B

Risk of coronary circulatory disease

high

high

Cause

ApoA5-Mutation

ApoE4-Mutation

Drug treatment

Not necessary

reasonable

Change in diet

Mediterranean nutrition: incl. animals kept in their natural environment red wine in moderation prefer food rich in Omega

no Mediterranean nutrition rich in dietary fibres not much fat a lot of fresh fruit a lot of fresh vegetables low glycaemic index prefer food rich in Omega 3

Supplementation

Omega 3 fatty acids

Smoking

no influence

abstinence

Alcohol

see med. nutrition

abstinence

Therapy control

LipoScan Fatty acid composition

LipoScan

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LipidGen – optimised genetic analysis of the lipid metabolism

PRINCIPLE OF ANALYTICS Real-time PCR

REFERENCES

FINDINGS The LipidGen findings provide information on the genetic profile of the fat metabolism and, together with the findings of LipoScan, metabolic function test, medical history sheet on disorders of the fat metabolism and other relevant laboratory diagnostic parameters such as e.g. homocysteine, LDLox, insulin, triglycerides, fatty acid composition, APOA1, and APOB as well as Lpa, on the risk of (coronary -> as even brain insult) heart and circulatory diseases. Based on these results, the findings include individual and optimised therapy recommendations regarding nutrition, lifestyle and medication.

THERAPY CONTROL r LipoScan r Fatty acid composition PREANALYTICS AND PERFORMANCE r Genes interact with the environment. The selection of the right gene test for the individual person is based on the results of LipoScan, a metabolic function test for fat metabolism and some information on the patient’s medical history. This helps saving unnecessary costs. r Taking of a blood sample and shipping: EDTA 3 ml, mailing without cooling possible

Contact

A laboratory service of:

Evomed MedizinService GmbH Heidelberger Landstraße 190 64297 Darmstadt Germany

Version: 30.09.2008

Phone +49 (0)6151- 666 800 Fax. +49 (0)6151- 666 801 info@evomed.com www.evomed.com

Nordic Laboratories InVitaLab Nordic Clinic, Hammfelddamm 6 Nygade 6, 3 sal., 41460 Neuss, Germany 1164 København K

Phone: +49 (0)2131-125969-0 E-mail: info@inivitalab.de www.invitalab.de

t Underexpression of the apolipoprotein E3 and E4 alleles in the greek cypriot population of Cyprus.

Cariolou M.A., et al. Clin. Gnet. 52(4):216218 (1997) Abstract: The epsilon4 allele frequency of 6.5% in the Greek population is, together with the frequency in the Chinese population, among the lowest in the world. t Women have a larger and less atherogenic low density lipoprotein particle size than men.

Nikkilä M. et al., J. Biomed. Sci. 10(3):345251 (2003) Abstract: There is a significant interaction between sex and age in serum total cholesterol which is highest in older women.

However, their LDL size is larger and their LDL is less atherogenic. ApoE phenotype has a significant influence on LDL size. t Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study.

Lahos, C. et al. Atherosclerosis.

154(3):529-37 (2001)