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. Clinical Pharmacology & Therapeutics (2006) 79 , 581–589; doi: 10.1016/j.clpt.2006.02.007