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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.

Original publication

DOI

10.1097/00004872-200402000-00015

Type

Journal article

Journal

Journal of hypertension

Publication Date

02/2004

Volume

22

Pages

313 - 319

Addresses

Departments of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands.

Keywords

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