Renin-angiotensin system polymorphisms and risk of hypertension: influence of environmental factors

Renin-angiotensin system (RAS) polymorphisms have been studied as candidate risk factors for hypertension with inconsistent results, possibly due to heterogeneity among various environmental factors. We analyzed the association between RAS candidate gene polymorphisms and risk of hypertension among 2722 women and also explored whether these associations varied according to menopausal status, body mass index, and dietary factors. In a main-effects analysis of all 2722 women adjusted for age and race, homozygosity for the AT1R A1166C polymorphism was associated with hypertension (odds ratio, 1.35; 95% confidence interval [CI], 1.03-1.78). We also found that a novel nonsense polymorphism in the aminopeptidase-A gene was associated with hypertension among postmenopausal women (hazard ratio, 1.54; 95% CI, 1.01-2.37), women with inadequate calcium intake (hazard ratio, 2.47; 95% CI, 1.29-4.72) and, marginally, women with inadequate vitamin D intake. In addition, angiotensin-converting enzyme and AT1R A1166C polymorphisms were associated or marginally associated with incident hypertension among postmenopausal women and those with inadequate calcium and vitamin D intakes. These data suggest that demographic and dietary factors may influence the associations between RAS polymorphisms and hypertension and could explain heterogeneity in prior studies.