Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy

Ann Pharmacother. 2006 Feb;40(2):212-8. doi: 10.1345/aph.1G316. Epub 2006 Jan 31.

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, beta-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, beta-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% CI -5.48 to 5.94) for diuretics, -2.41 mm Hg (95% CI -6.72 to 1.90) for beta-blockers, 2.12 mm Hg (95% CI -4.64 to 8.89) for calcium-channel antagonists, and -2.01 mm Hg (95% CI -9.82 to 5.79) for ACE inhibitors.

Conclusions: The adjusted mean difference in diastolic and systolic blood pressure among diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by the ACE insertion/deletion polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Blood Pressure / genetics
  • Female
  • Follow-Up Studies
  • Gene Deletion
  • Genotype
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / enzymology
  • Hypertension / genetics
  • Male
  • Mutagenesis, Insertional
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Prospective Studies
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Peptidyl-Dipeptidase A