Associations between CYP11B2 gene polymorphisms and the response to angiotensin-converting enzyme inhibitors

Clin Pharmacol Ther. 2006 Jun;79(6):581-9. doi: 10.1016/j.clpt.2006.02.007.

Abstract

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / blood
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Asian People / genetics
  • Benzazepines / administration & dosage
  • Benzazepines / blood
  • Benzazepines / pharmacokinetics
  • Benzazepines / pharmacology
  • Blood Pressure / drug effects*
  • China
  • Cytochrome P-450 CYP11B2 / genetics*
  • Female
  • Humans
  • Hypertension / drug therapy
  • Hypertension / genetics*
  • Hypertension / pathology
  • Imidazolidines / administration & dosage
  • Imidazolidines / blood
  • Imidazolidines / pharmacokinetics
  • Imidazolidines / pharmacology
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Severity of Illness Index
  • Single-Blind Method

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Imidazolidines
  • imidapril
  • Cytochrome P-450 CYP11B2
  • benazepril