OS 08-03 PHARMACOGENETIC MARKERS OF SURVIVAL.

OBJECTIVE: Physiological and biochemical changes during aging alter drug metabolism. Drug intake is increased with age because of cumulative morbidity, in particular, high prevalence of cardiovascular diseases. Antihypertensive medications are the most commonly used drugs. Individual drug sensitivity or resistance may be influenced by the variance of the "pharmacological response" genes.Our purpose was to search for the polymorphic variants of "pharmacological response" genes associated with survival in different age periods.

DESIGN AND METHOD: The study group consisted of 832 healthy persons aged between 21 and 109 years from the Republic of Bashkortostan (Russia). Participants were divided into three age subgroups: middle-age, elderly and long-livers. Polymorphic markers of ITGB3 (rs5918), ABCB1 (rs1045642), PTGS1 (rs3842787), PTGS2 (rs20417), F5 (rs6025) and VKORC1 (rs9934438) genes were analyzed by PCR method. Statistical analysis was performed using IBM SPSS V.21.0.

RESULTS: ABCB1Т allele was detected with high frequency (58.87%) in the study group, comparable to the majority of Caucasian populations. ABCB1Т allele is associated with increased absorption and slow excretion of xenobiotics, and therefore testing for this polymorphism is important for selecting medications and dosage. Similarly high frequency of PTGS2 C allele was observed in the study group (18.63%). PTGS2 C allele is associated with aspirin resistance, which makes it an important pharmacogenetic marker. ITGB3*C allele frequency was decreased in the elderly subgroup compared to the middle-age subgroup (6.44% vs. 17.95%, p = 0.0003). ITGB3 C allele is associated with low response to anticoagulants, and the carriers of ITGB3 C allele have an increased risk of myocardial infarction, stroke, sudden cardiac death, hypertension. Thus, we suggest that the frequency of ITGB3 C allele is diminished with age due to negative selection.

CONCLUSIONS: The results of our study demonstrate the age-related trend for decreased frequency of polymorphic markers associated with impaired sensitivity to anticoagulants.