Intron-2 conversion polymorphism of the aldosterone synthase gene and the antihypertensive response to angiotensin-converting enzyme inhibitors

Abstract

Aldosterone controls sodium balance and intravascular volume, and thus helps regulate blood pressure. Secretion of aldosterone is mainly regulated at the level of expression of the aldosterone synthase (CYP11B2) gene. The intron-2 conversion polymorphism of CYP11B2 was suggested to lead to overexpression of the gene, and may therefore have potential to predict the blood pressure response of patients with essential hypertension to angiotensin-converting enzyme inhibitors (ACEIs). To investigate the association between the intron-2 conversion polymorphism and the blood pressure response to ACEIs in a hypertensive cohort. After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. The intron-2 conversion polymorphism was examined by polymerase chain reaction. The IwIw genotype was observed in 106 patients (20.8%), the IwIc genotype in 251 patients (49.3%), and the IcIc genotype in 152 patients (29.9%). After 6 weeks of treatment the reductions in diastolic blood pressure were significantly greater in patients carrying IcIc or IwIc compared with IwIw genotypes (9.2 +/- 7.2 or 9.2 +/- 7.1 versus 6.4 +/- 6.6 mmHg, respectively; analysis of variance, P = 0.001). Stepwise multiple regression analysis showed that significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P < 0.001), intron-2 conversion genotype (P = 0.006) and sex (P = 0.030). The intron-2 conversion polymorphism was related to the diastolic blood pressure lowering response in hypertensive patients treated with ACEIs. Interindividual variation in the efficacy of antihypertensive medications may therefore be influenced by genetic factors.