Polygenic association of the renin-angiotensinaldosterone system polymorphisms in essential arterial hypertension

Abstract

Objective. To determine the polygenic association of polymorphisms of M235T angiotensinogen (AGT) gene, I/D angiotensin-converting enzyme (ACE) gene, C3123A of angiotensin II type 2 receptor gene (AGTR2), C344T aldosterone synthase gene (CYP11B2) with essential arterial hypertension (HTN). Design and methods. A total of 532 subjects are examined, representing the Belarussian ethnic homogeneous group (356 hypertensive patients and 176 normotensives). Clinical and molecular genetic examinations of the renin-angiotensinaldosterone system (RAAS) polymorphisms were performed. The search and analysis of polygenic associations are implemented using APSampler software. Results. We found an association of the combined polymorphisms of T allele of gene AGT (M235T) and T allele of gene CYP11B2 (C344T) with essential HTN in women under 45 years (odds ratio, OR = 4,15, 95 % confidence interval, CI = 1,90–9,07; р = 0,004). Polygenic associations among normotensives included: I allele (I/D) ACE gene and CC genotype (C3123A) AGTR2 gene (OR = 0,58; 95 % CI = 0,49–0,68; р = 0,03); I allele (I/D) ACE genes and ММ genotype (М235 Т) of AGT gene in women under 45 years (OR = 0,09; 95 % CI = 0,01–0,63; р = 0,005); М allele (М235 Т) of AGT gene and CC genotype (C3123A) of AGTR2 gene in all subjects over 45 years (OR = 0,55; 95 % CI = 0,47–0,64; р = 0,03). Conclusions. There was no difference in distribution of the studied alleles and genotypes of RAAS genes in patients with HTN and healthy subjects. At the same time the polygenic combinations of RAAS genetic polymorphisms significantly differ between hypertensive and normotensive subjects. This indicates the advantages of studying the effect of combinations of genotypes and/or alleles of different polymorphic loci on the risk of essential HTN before analyzing the impact of each single locus.