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 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.
Fan
X
X
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.
Wang
Y
Y
Sun
K
K
Zhang
W
W
Yang
X
X
Wang
S
S
Zhen
Y
Y
Wang
J
J
Li
W
W
Han
Y
Y
Liu
T
T
Wang
X
X
Chen
J
J
Wu
H
H
Hui
R
R
D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D002216:Captopril / Q000627:therapeutic use*; D016022:Case-Control Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000379:methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D000959:Antihypertensive Agents; D001786:Blood Glucose; D008055:Lipids; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2