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

Author(s): Fan X, Wang Y, Sun K, Zhang W, Yang X, Wang S, Zhen Y, Wang J, Li W, Han Y, Liu T, Wang X, Chen J, Wu H, Hui R, Study Group for Pharmacogenomic Based Antihypertensive Drugs Selection, Effects and Side Effects, in Rural Area Chinese

Affiliation(s): Hypertension Division, Department of Cardiology, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Publication date & source: 2007-08, Clin Pharmacol Ther., 82(2):187-96. Epub 2007 May 2.

Publication type: Research Support, Non-U.S. Gov't

ACE2 appears to counterbalance the vasopressor effect of angiotensin I converting enzyme (ACE) in the reninangiotensin 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 casecontrol 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), 1.132.06), whereas when combined with the effect of the ACE DD genotype, the risk was 2.34-fold (95% CI, 1.754.85) in two independent samples. The adjusted diastolic blood pressure response to Captopril was 3.3 mm 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.