Polygenic analysis of genetic susceptibility to essential hypertension

Abstract

Objective. To investigate the molecular mechanism underlying genetic susceptibility to essential hypertension (EH) using polygenic analysis of renin-angiotensin-aldosterone system (RAAS).Design and methods.Genotyping of renin (REN, rs2368564), angiotensinogen (AGT, rs4762), angiotensin II receptor type 1 (AGTR1, rs5186), chymase 1 (CMA1, rs1800875) and angiotensin-converting enzyme (ACE, rs1799752) polymorphic variants was performed in 346 patients with EH and 377 controls, Russians and Tatars by ethnic origin.Results. ACE rs1799752polymorphism was significantly associated with EH risk in Tatars (PBonf= 0,003) and in the total study group (PBonf= 4,09 x 10–5). Polygenic approach identified 12 genotypes and/or alleles combinations of RAAS genes polymorphisms, significantly associated with EH in the Tatars, and 6 patterns associated with EH in the total study group. The highest risk of disease in Tatar men was associated with REN rs2368564*T + AGTR1 rs5186*C/A + ACE rs1799752*D combination (OR = 16,64, PBonf= 0,001), in the total group — with REN rs2368564*T/C + CMA1 rs1800875*G combination (OR = 2,37, PBonf= 0,045).Conclusions. Our findings indicate that EH risk in men of Russian and Tatar ethnicity is significantly associated with ACE rs1799752 polymorphism, and the results of polygenic analysis demonstrate an association of the disease risk with genotype/allele combinations of polymorphic variants in REN (rs2368564), AGTR1 (rs5186), ACE (rs1799752), and CMA1 (rs1800875) genes.