Structural and functional condition of the heart in patients with arterial hypertension depending on A1166C-gene polymorphism of angiotensin II type 1 and T786C-promoter of endothelial NO-synthase gene

Abstract

It's known that pathological changes in structural and functional condition of the heart, which are caused by arterial hypertension, trigger development of chronic heart failure and disablement of population. Nowadays, it proven that candidate genes, expression products of which participate in regulating vascular tone, have considerable influence upon development of arterial hypertension, however their role in pathogenesis of arterial hypertension has not been fully clarified, and results of the respective researches significantly vary among different populations. To determine the structural and functional state of the heart in patients with hypertension depending on the polymorphism of the A1116C gene of the angiotensin II receptor type I and the T786C promoter of the endothelial NO-synthase gene we examined 86 patients, aged from 45 to 76 years. 30 people without signs of hypertension were in the control group. The structural and functional state of the heart was assessed by cardiac ultrasound according to standard methods. Studies of the A1166C allelic polymorphism of the angiotensin II receptor gene type 1 and the T786C promoter of the eNOS gene were performed by polymerase chain reaction with electrophoretic detection of results. Analysis of cardiac ultrasound showed, that in the patients – carriers of C-allele of both studied genes (AС+СС and TC+CC) left ventricular ejection fraction tended to decrease. We found a bigger thickness of the posterior wall of the left ventricle in patients with CC genotype compared to carriers of AA genotype A1166C – (1.3±0.07) cm vs. (1.1±0.05) cm (p<0.005). The mass of the left ventricular myocardium index in the group of patients with the genotype AC and CC was (157.5±7.3) g/m2 and (161.5±7.1)) g/m2, respectively, being by 16.7% and 19.6% more than in carriers of AA genotype of the AGTR1 gene. In the groups of patients-carriers of C-allele (TC+CC) of the eNOS gene the mass of the left ventricular myocardium index values were (155.2±11.4)) g/m2 and (158.4±7.9)) g/m2, respectively, which is by 5.4% and 7.5% more than in carriers of TT genotype. The mean size of the left atrium was significantly higher in patients who had AC and CC genotype of the AGTR1 gene, as well as TC and CC genotype of the eNOS gene compared with the control group. Carriers of C-allele (AC+CC genotype) of AGTR1 gene polymorphism had clearly bigger sizes of the left atrium, as compared to homozygotes by A-allele. The severity of diastolic dysfunction was higher in carriers of the CC genotype of the AGTR1 gene and the eNOS gene than in heterozygotes of the studied genes by 4.3% and 3.3%, respectively. The research shows that inheritance of CC genotype for A1166C polymorphism of the the angiotensin II type 1 receptor gene and of CC T786C polymorphism in the promoter of eNOS gene is associated with more noticeable changes in structural and functional heart condition among patients with arterial hypertension.