Significance of angiotensinogen gene haplotypes and genotypes combinations in hypertension.
OBJECTIVE
Renin-angiotensin system gene polymorphisms are associated with essential hypertension; angiotensinogen gene variants are considered potential genetic risk factors. The aim of this study was to investigate the contribution of the G-6A, T174M, M235T polymorphisms, genotypic interactions, and haplotypes toward essential hypertension.


METHODS
In a case-control design, 810 consecutive ethnically matched unrelated individuals comprising 450 hypertensive patients and 360 controls were recruited. Genotyping by polymerase chain reaction-restriction fragment length polymorphism, genotypes combinations, and haplotypes analyses were performed. Plasma renin activity and plasma aldosterone concentration were measured.


RESULTS
The G-6A and M235T polymorphisms differed significantly (P = 0.007, odds ratio = 1.9, 95% confidence interval = 1.2-2.9; P < 0.0001, odds ratio = 3.7, 95% confidence interval = 2.3-5.7, respectively), wherein the -6A and 235T mutant alleles were over-represented in hypertensive patients (P < 0.0001, each). Genotypes combinations of six wild-type alleles versus the remaining resulted in odds ratio of 2.4 (P < 0.0001), further mutant alleles based combinations linearly correlated with systolic, diastolic, and mean blood pressure. Over-representation of the haplotypes, namely, A/174T, 174T/235T, A/235T, and A/174T/235T in hypertensive patients and G/174T, 174T/235M, G/235M, and G/174T/235M in controls, was identified as risk and protective haplotypes (P < 0.0001, each), respectively. The patients had significantly higher plasma aldosterone concentration and lower plasma renin activity (P < 0.0001), the former correlated with -6A and 235T alleles (P < 0.0001).


CONCLUSIONS
The interaction among G-6A, M235T and T174M polymorphisms in combinations or haplotypes emerged significant. These findings, conjoint with significant high plasma aldosterone concentration and low plasma renin activity, suggest low-renin hypertension in our study population.
Nejatizadeh
Azim
A
Institute of Genomics and Integrative Biology, India.
Kumar
Rahul
R
Stobdan
Tsering
T
Goyal
Ajit K
AK
Gupta
Mohit
M
Javed
Saleem
S
Pasha
Ma Qadar
MQ
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000808:Angiotensinogen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012083:Renin / Q000097:blood
D000808:Angiotensinogen; D000450:Aldosterone; D012083:Renin