From Genetic Testing to Personalized Approach in Patients Dr. Amirova Т.О. Prof. Bernard WEBER
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1 From Genetic Testing to Personalized Approach in Patients Dr. Amirova Т.О. Prof. Bernard WEBER
2 Genome-oriented Medicine What is possible today. Analyze Genetic Variations that influence - disease susceptibility - disease progression - therapeutic response - unwanted drug reactions (!)The use of known genetic variations for diagnostic purposes and targeted treatment
3 Contributions of genetic and environmental factors to human diseases Cystic fibrosis Asthma Hemophilia Schizophrenia T2DM Stroke Skin diseses Lung Cancer GENETIC ENVIRONMENTAL Bipolar disorder Cardiovascular disease Motor vehicle accident Familial Colon or Breast Cancer Rare Genetics simple Unifactorial High recurrence rate Common Genetics complex Multifactorial Low recurrence rate
4 Genetic variation in SNPs (Single Nucleotide Polymorphisms) ATTGCAATCCGTGG...ATCGAGCCA TACGATTGCACGCCG ATTGCAAGCCGTGG...ATCTAGCCA TACGATTGCAAGCCG ATTGCAAGCCGTGG...ATCTAGCCA TACGATTGCAAGCCG ATTGCAATCCGTGG...ATCGAGCCA TACGATTGCACGCCG ATTGCAAGCCGTGG...ATCTAGCCA TACGATTGCAAGCCG
5 Single genetic risk factors identified are of limited use in multifactorial diseases Fails to take into account gene-environment interactions Fails to take into account gene-gene interactions Need to understand genetics at a systems-level Analyse PANELS Selected SNP are based on GWAS or meta-analyses
6 Preventive genetics Multifactorial Interactions between environment and genes Gene expression can be influenced Accessible to «every» physician for personalized prevention Nutrigenetics Ecogenetics Toxicogenetics Pharmacogenetics Psychogenetics Immunogenetics INTERACTION
7 Keys for the Interpretation of Preventive Genetics Susceptibility genes represent tendencies in most of the cases Most of the people do not have a prostate cancer or Alzheimer s disease gene There are genes that increase the susceptibility to cancer or degenerative diseases If the wrong lifestyle choice is made The outcome can be changed by proper lifestyle choices
8 Genomics and Epigenetics Epigenetics : Heritable genetic modifications,e.g. DNA methylation, histone Deacetylation, that are not attributable to changes in the primary DNA sequence Key role in the regulation of gene expression,critical to the development, regulation and maintenance of the cell
9 Methylation Methylation Increased Expression Silencing
10 and health Genomics Proteomics Metabolomics (Gene Expression) (Protein Synthesis) (Nutrient Modulation) Positive health outcome
11 Global expression analysis allows us to assign a molecular signature to a biological state Stress Trauma; Infect. Disease Clinical Disease Pre-disease state Exposure to Toxines We can develop knowledge to understand causes of disease and susceptibility to disease.then we can develop ways to prevent or treat disease
12 Personalized Report, based on genetic variations. Data on personal and familial risk factors, diseases, nutrition and lifestyle are essential for nutrigenetic interpretation and recommendations The choice of genetic markers needs to be based on age, sex, lifestyle, familial and personal history and clinical and laboratory findings Consider only gene variants that have a clinical validity and utility The Interpretation of genetic test profiles needs to be based on gene-gene and geneenvironment interactions and provide practical recommendations on lifestyle changes, nutrition and micronutrition Use phenotypic markers for base-line and follow-up testing Nutrigenomics Lifestyle Pharmacogenetics 12
13 Report. Example. We group analyzed polymorphisms in accordance with certain metabolic pathways involved. Амирова Т.О. 13
14 Амирова Т.О. 14
15 CARDIOgen profile - Effects of the analysed variations Endothelial NO-synthase activity Paraoxonase 1 activity Relative risk for coronary diseases Renin-aldosterone system activity Angiotensinogen synthesis Na reabsorption Renin levels Relative risk for hypertension Methylenetetrahydrofolate reductase activity 5 -methyltetrahydrofolate homocysteine methyl-transferase Methionine synthase reductase Relative risk for increased Hcy levels
16 Nutri- and pharmacogenetical recommendations Omega-3 fatty acids (fatty fish, nuts, olive oil) enos activity and expression CARDIOgen profile enos - Recommendation (nutrition) Effect Recommendations (drugs) Vitamin B9 (dark green leafy vegetables, citrus fruits...) MTHFR PON1 Lycopene (tomato derived Recommendatio Effect products), polyphenols (e.g. ns (nutrition) resveratrol) PON1 Recommendations stimulation (drugs) MTR MTRR Vitamins B6, B9 Increased Prevent a and ACE Recommendations B12 toxicity (nutrition) / vitamin Effect B Recommendations (drugs) (contained in unwanted deficiency legumes, green effects of ( leafy MTHFR increased vegetables...) Omega-3 fatty acids substrates (fatty fish, (e.g. Hcy levels) angiotensin nuts, olive oil) Methotrexate) II induced hypertension AGT Prevent Resveratrol a (to be found in dark strictly red grapes, red wine...) vegetarien diet Catechins (contained in green tea) ADD1 White tea extracts, polyunsaturated fatty acids ADD1 expression risk for myocardial infarction if ACE inhibitors GNB3 Reduced salt intake Hypertension Best efficiency: thiazidic diuretics, clonidine
17 CARDIOgen profile - Effects of the analysed variations Plasma prothrombin levels Resistance to activated protein C Thrombocyte aggregation Fibrinolytic activity Relative risk for thrombosis Serum IgE Excessive IgE production Inflammation
18 CARDIOgen profile - Nutri- and pharmacogenetical recommendations Factor II Recommendations (nutrition) Effect Recommendations (drugs) Factor V Allicine, S-allyl-cysteine, alliine, ajoene, saponins, flavonoids, rutin, caffeine Thrombocyte aggregation GP3A Allicine, S-allyl-cysteine, alliine, ajoene (contained in aged garlic) Antiplatelet activity Response to antiplatelet drugs (e.g. Aspirine) PAI Monounsaturated fatty acids (to be found in dietary oils such as pecan, peanut, or poppyseed oil) PAI levels IL-4 Effect Recommendations (drugs) SELP Vitamin B9 (dietary yeast, peas, soy products...), vitamin E (sunflower seeds, paprika, almonds...) IgE levels
19 LR-Genomics
20 LR-Genomics
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