Significance of angiotensinogen gene haplotypes and genotypes combinations in hypertension

J Hypertens. 2008 Jun;26(6):1094-101. doi: 10.1097/HJH.0b013e3282fad951.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldosterone / blood
  • Angiotensinogen / genetics*
  • Case-Control Studies
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Hypertension / blood
  • Hypertension / genetics*
  • India
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Renin / blood


  • Angiotensinogen
  • Aldosterone
  • Renin