Drug-Gene Interaction Between the Insertion/Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Antihypertensive Therapy

Abstract

Background: Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive. Objective: To investigate whether the insertion/deletion polymorphism of the ACE gene modifies blood pressure differences among subjects using diuretics, β-blockers, calcium-channel antagonists, or ACE inhibitors. Methods: Data were used from the Rotterdam Study, a population-based, prospective, cohort study in the Netherlands, which started in 1990 and included 7983 subjects aged 55 years or older. Data from 3 subsequent cross-sectional investigations were used, as well. Subjects were included if they had high blood pressure during one or more examinations and/or used monotherapy with a diuretic, β-blocker, calcium-channel antagonist, or ACE inhibitor. A marginal, generalized, linear model was used to assess the association between the mean difference in systolic/diastolic blood pressure and antihypertensive classes stratified by the 3 genotypes. Results: In total, 3025 hypertensive individuals were included, and 6500 measurements of blood pressure were taken. The percentages of DD, ID, and II genotypes were 28.3%, 51.4%, and 20.3%, respectively. The mean differences in systolic blood pressure between the II and DD genotypes were 0.23 mm Hg (95% Cl −5.48 to 5.94) for diuretics, −2.41 mm Hg (95% Cl −6.72 to 1.90) for β-blockers, 2.12 mm Hg (95% Cl −4.64 to 8.89) for calcium-channel antagonists, and −2.01 mm Hg (95% Cl −9.82 to 5.79) for ACE inhibitors. Conclusions: The adjusted mean difference in diastolic and systolic blood pressure among diuretic, β-blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by the ACE insertion/deletion polymorphism.