Associations between CYP11B2 gene polymorphisms and the response to angiotensin-converting enzyme inhibitors.
OBJECTIVE
Our objective was to investigate the association between the -344C/T or A6547G polymorphism of the aldosterone synthase gene and the blood pressure response to angiotensin-converting enzyme inhibitors in a hypertensive cohort.


METHODS
After a 2-week single-blind placebo run-in period, either benazepril or imidapril was administered for 6 weeks to 509 patients with mild to moderate essential hypertension. Polymerase chain reaction combined with restriction enzyme digestion was used to detect the 2 polymorphisms. The achieved changes in systolic and diastolic blood pressure were analyzed for their association with genotypes at the aldosterone synthase gene loci.


RESULTS
Regarding the -344C/T polymorphism, we observed the CC genotype in 53 patients (10.4%), the CT genotype in 204 (40.1%), and the TT genotype in 252 (49.5%). After 6 weeks of treatment, the reductions in diastolic blood pressure were significantly greater in patients carrying the TT or CT genotype compared with those carrying the CC genotype (9.1+/-7.0 mm Hg or 8.9+/-7.0 mm Hg versus 5.1+/-7.3 mm Hg, respectively; P=.001, ANOVA). Regarding the A6547G polymorphism, we observed the AA genotype in 19 patients (3.7%), the AG genotype in 184 (36.2%), and the GG genotype in 306 (60.1%). There were no significant differences in the blood pressure reductions after treatment among the 3 genotype groups, and there was no interaction between it and the -344C/T polymorphism. Stepwise multiple regression analysis showed that the significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P<.001), -344C/T genotype (P=.007), and sex (P=.033).


CONCLUSIONS
The -344C/T variant, but not the A6547G variant, of the aldosterone synthase gene may be a determinant of the blood pressure response to angiotensin-converting enzyme inhibitors in hypertensive patients.
Yu
Hui-Min
HM
Department of Cardiology, Guangdong Provincial People's Hospital and Guangdong Cardiovascular Institute, Guangzhou, China.
Lin
Shu-Guang
SG
Liu
Guo-Zhang
GZ
Zhang
Yu-Qing
YQ
Ma
Wen-Jun
WJ
Deng
Chun-Yu
CY
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D044466:Asian People / Q000235:genetics; D001552:Benzazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002681:China; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D048289:Imidazolidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D016037:Single-Blind Method
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D048289:Imidazolidines; C065166:imidapril; D019405:Cytochrome P-450 CYP11B2; C044946:benazepril