Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure.
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.
Schut
Anna F C
AF
Departments of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands.
Sayed-Tabatabaei
Fakhredin A
FA
Witteman
Jacqueline C M
JC
Avella
Aida M Bertoli
AM
Vergeer
Jeannette M
JM
Pols
Huibert A P
HA
Hofman
Albert
A
Deinum
Jaap
J
van Duijn
Cornelia M
CM
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000235:genetics*; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*; D013599:Systole
D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A