Association study of eight candidate genes with renin status in mild-to-moderate hypertension in patients of African ancestry

Abstract

Aim. We evaluated whether anyone variant of genes that encode for substances that could modulate renin-angiotensin-aldosterone (RAA) system activity can account for a substantial proportion of the variability of plasma RAA system profiles in black South African hypertensives (HTs). Methods. Plasma renin activity (PRA) and aldos-terone concentrations (ALD) were determined in 59 black subjects with mild-to-moderate HT ofT therapy onan ad libitum diet. Patients were genotyped for the angiotensin-converting enzyme (ACE) gene insertion/deletion, angiotensinogen (AGT) gene M235T, A-20C and G-6A, aldosterone synthase (CYPllB2) gene C-344T, G protein P3-subunit (GNB3) gene C825T, Gs protein gene C13! T, atrial natriuretic peptide (ANP) gene exon 3 stop codon and intron 2, a-adducin gene Gly460Trp, and epithelial Na+ channel (eNa+c) gene T594M polymorphisms. Results. Risk genotype frequencies for the G, (7%), ANP intron 2 (0%), and eNa+c (7%) variants were too low for each to account for a substantial portion of the variability of plasma RAA profiles in the group studied. Moreover, assuming either recessive or dominant inheri-tance models, neither ACE, AGT, GNB3, CYPllB2, ANP exon 3 nor a-adducin polymorphisms were signifi-cantly associated with the variance of PRA, ALD or ALDIPRA. Conclusions. These results do not support a substan-tial individual role for the gene candidates studied in contributing to plasma RAA system profiles in black South African HTs. However, a potential small role for some loci may exist, and epistasis or genotype-phenotype interactions as well as alternative inheritance models and variants still need to be evaluated.