Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of captopril in women

ACE2 appears to counterbalance the vasopressor effect of angiotensin I converting enzyme (ACE) in the renin-angiotensin system. We hypothesized that ACE2 polymorphisms could confer a high risk of hypertension and have an impact on the antihypertensive response to ACE inhibitors. The hypothesis was tested in two case-control studies and a clinical trial of 3,408 untreated hypertensive patients randomized to Atenolol, Hydrochlorothiazide, Captopril, or Nifedipine treatments for 4 weeks. ACE2 rs2106809 T allele was found to confer a 1.6-fold risk for hypertension in women (95% confidence interval (CI), 1.13-2.06), whereas when combined with the effect of the ACE DD genotype, the risk was 2.34-fold (95% CI, 1.75-4.85) in two independent samples. The adjusted diastolic blood pressure response to Captopril was 3.3mm Hg lower in ACE2 T allele carriers than in CC genotype carriers (P = 0.019) in women. We conclude that the ACE2 T allele confers a high risk for hypertension and reduced antihypertensive response to ACE inhibitors.