Significance of angiotensinogen gene haplotypes and genotypes combinations in hypertension

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Abstract

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).

Conclusion

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.

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