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.

Angiotensin-converting enzyme, Blood pressure, Genes, Hypertension, Smoking
dx.doi.org/10.1097/00004872-200402000-00015, hdl.handle.net/1765/60628
Journal of Hypertension
Erasmus MC: University Medical Center Rotterdam

Schut, A.F.C, Sayed-Tabatabaei, F.A, Witteman, J.C.M, Bertoli Avella, A.M, Vergeer, J.M, Pols, H.A.P, … van Duijn, C.M. (2004). Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure. Journal of Hypertension, 22(2), 313–319. doi:10.1097/00004872-200402000-00015