OS 08-03 PHARMACOGENETIC MARKERS OF SURVIVAL

Vera Erdman, Ilsia Tuktarova, Timur Nasibullin, Ianina Timasheva, Olga Mustafina
2016 Journal of Hypertension  
Objective: Hypertension (HTN) is the most common cardiovascular disease and is assuming epidemic proportions in developing countries. Genetic and environmental factors play important role in the development of hypertension.The objective of this study was to investigate the possible association of ACE, FABP2, PPARG2, GST, FTO and CYP46A1 genes polymorphism and susceptibility of individuals to HTN. Design and method: This case control study includes 123 essential HTN cases and 102 controls. ACE,
more » ... ST genes polymorphisms were evaluated by PCR and FABP2, PPARG2, FTO, CYP46A1 genes polymorphisms were evaluated by PCR-RFLP methods. Results: The mean age of cases and controls were 41.32 ± 11.39 years and 40.13 ± 10.28 years. Frequencies of ACE II, ID, DD genotypes in essential HTN cases and controls were 22.76%, 63.42%, 13.82% and 11.77%, 60.78%, 27.45%; respectively. Frequencies of FABP2 AA, AT, TT in cases and controls were 11.38%, 70.74%, 17.88% and 20.59%, 64.71%, 14.70%. Frequencies of PPARG2 CC, CG, GG genotype in cases and control were 27.65%, 65.85%, 6.50% and 21.57%, 37.26%, 41.17%. Frequency of GSTM1 null, GSTT1 null genotypes in cases and controls were 41.47%, 5.69% and 52.95%, 4%; respectively. Frequencies of FTO AA, AT, TT genotype in cases and control were 1.63%, 68.29%, 30.08% and NA, 75.49%, 24.51%. Frequencies of CYP46A1 CC, CT, TT genotype in cases and control were 17.08%, 33.33%, 49.59% and 3.93%, 28.43%, 67.64%. Signifi cant differences were obtained in the frequencies of ACE II genotype (p = 0.032), PPARG2 CG, GG genotype (p < 0.001) CYP46A1 CC, TT genotype (p = 0.002, 0.006). Conclusions: Findings of this study suggest that ACE, PPARG2, CYP46A1 genes were signifi cantly associated with essential HTN cases in North Indian populations. Objective: Apelin activity plays a role in regulating blood pressure. This study explored the relationship between single nucleotide polymorphisms (SNPs) in the Apelin gene (APLN) with hypertension and hypertension with central retinal artery equivalent (CRAE) stenosis in a coastal Chinese population. Design and method: All subjects answered an epidemiological survey for demographic and disease characteristics. Apelin levels were determined and three APLN SNPs, rs56204867, rs3115757, and rs3761581, were evaluated. CRAE was measured using fundus photography. Results: Apelin levels were signifi cantly lower in subjects with hypertension and hypertension with CRAE stenosis (0.23 ± 0.10 ng/ml and 0.21 ± 0.08 ng/ml, respectively) compared with control subjects (0.25 ± 0.11 ng/ml; p50.001). Linear regression analysis showed hypertension and hypertension with CRAE stenosis was associated with age, being male, systolic blood pressure, abnormal blood lipids, and Apelin levels. Genetic analysis indicated that in both males and females SNP rs3761581 was associated with hypertension and that more males carrying rs56204867 and rs3761581 T-A haplotype had hypertension (61.88%) and hypertension with CRAE stenosis (56.82%) than control males (39.33%). Conclusions: In this Chinese population, Apelin and APLN SNP rs3761581 was associated with combined hypertension with CRAE, indicating that the expression of APLN gene products may be involved in vascular injury. 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 infl uenced 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: ABCB1*T allele was detected with high frequency (58.87%) in the study group, comparable to the majority of Caucasian populations. ABCB1*T 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. Objective: Genes encoding key elements of the renin-angiotensin-aldosterone system (RAAS) cascade have been previously but inconsistently associated with blood pressure. Sex-dependency might be important here and functional genetic polymorphisms might exhibit epistatic effects.
doi:10.1097/01.hjh.0000500028.22615.da fatcat:rjghatejtjcpfdn4qxyqmamine