Renin polymorphisms and haplotypes are associated with blood pressure levels and hypertension risk in postmenopausal women.

Background: Renin is a key protein of the renin-angiotensin system involved in the physiological control of blood pressure; the renin gene is therefore a candidate for essential hypertension in humans. We tested the association between polymorphisms and haplotypes of the renin gene and the risk of hypertension and blood pressure levels in two Spanish populations.

Methods: Two population-based studies from different regions of Spain were performed. Study A included 1502 individuals (748 women) 40-70 years old, and Study B included 670 women 45-70 years old. Fourteen polymorphisms of the renin gene were selected based on position, spacing, heterozygosity (> 10% for the minor allele frequency) and previous information, and were assessed by SNPlex.

Results: Genotype GG of the rs5707 polymorphism was significantly associated with blood pressure levels (P = 0.005) and with the risk of having hypertension (odds ratio, 6.16; 95% confidence interval, 1.19-31.8) in women 40-70 years old from study A, but not the men. This association was also present in the women of study B (P < 0.001 for blood pressure values; odds ratio, 2.11 and 95% confidence interval, 1.07-4.17 for hypertension). Two haplotypes defined by five selected polymorphisms were associated with increased risk of hypertension in these aged women.

Conclusion: Polymorphisms of the renin gene were associated with blood pressure levels and risk of hypertension in women over 40 years old. The interaction between the potential functional impact of this genetic background and the estrogen fall could explain the association in women of this age group.