Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure

J Hypertens. 2004 Feb;22(2):313-9. doi: 10.1097/00004872-200402000-00015.


Background: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease.

Objective: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort.

Methods: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication.

Results: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele.

Conclusions: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Pressure / genetics*
  • DNA Transposable Elements*
  • Female
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote
  • Humans
  • Hypertension / etiology
  • Hypertension / genetics*
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Smoking / adverse effects*
  • Systole


  • DNA Transposable Elements
  • Peptidyl-Dipeptidase A