Association study of eight candidate genes with renin status in mild-to-moderate hypertension in patients of African ancestry.
OBJECTIVE
We evaluated whether any one 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 aldosterone concentrations (ALD) were determined in 59 black subjects with mild-to-moderate HT off therapy on an 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 (CYP11B2) gene C-344T, G protein beta3-subunit (GNB3) gene C825T, G(s) protein gene C131T, atrial natriuretic peptide (ANP) gene exon 3 stop condon and intron 2, alpha-adducin gene Gly460Trp, and epithelial Na(+) channel (eNa(+) (c)) gene T594M polymorphisms.


RESULTS
Risk genotype frequencies for the G(s) (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 inheritance models, neither ACE, AGT, GNB3, CYP11B2, ANP exon 3 nor alpha-adducin polymorphisms were significantly associated with the variance of PRA, ALD or ALD/PRA.


CONCLUSIONS
These results do not support a substantial 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.
Tiago
A D
AD
Cardiovascular Genomics Research Unit, Departments of Physiology and Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Nkeh
B
B
Candy
G P
GP
Badenhorst
D
D
Defterios
D
D
Brooksbank
R
R
Nejthardt
M
M
Luker
F
F
Milne
J
J
Woodiwiss
A J
AJ
Norton
G R
GR
D000450:Aldosterone / Q000097:blood / Q000235:genetics; D044383:Black People / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology*; D013019:South Africa / Q000208:ethnology
D000450:Aldosterone; D012083:Renin