Effect of CYP1A1 MspI polymorphism on cigarette smoking related coronary artery disease and diabetes.
CYP1A1, is one of the key detoxifying enzymes catabolizing cigarette smoking derived toxins and may be relevant to smoking-induced atherogenesis. Recently a CYP1A1 MspI polymorphism at the 3'-flanking region of the gene has been found to be associated with smoking related cancer risk and may, therefore, also be associated with vascular disease. To explore this, we investigated interactive effects between smoking and the CYP1A1 MspI polymorphism on coronary artery disease (CAD), diabetes and hypertension in 701 patients (aged < or =65 years) consecutively referred to Eastern Heart Clinic for angiographic investigation. The frequencies of the TT (80.2%), TC (17.7%) and CC (2.1%) genotypes were in Hardy-Weinberg equilibrium with the rare C allele frequency 0.11. The C allele carriers had an increased risk for triple vessel disease (three major epicardial coronary arteries with > or =50% luminal obstruction, OR, 3.44; 95%CI, 1.46-8.09; P=0.0046) in light smokers (< or =20 packyears). We further identified an interactive effect between smoking, the CYP1A1 MspI polymorphism and type 2 diabetes (chi(2)=9.508, P=0.002). The C allele carriers who were smokers had an increased risk of diabetes (OR, 2.44; 95%CI, 1.32-4.49; P=0.0059). Our study suggests that CYP1A1 may participate in the pathogenesis of atherosclerosis and in the development of diabetes and its vascular complications. The presence of the rare C allele of the CYP1A1 gene in smokers may enhance predisposition to severe CAD and type 2 diabetes. These findings contribute to the understanding of cardiovascular risk and to smoking related vascular disease.
Wang
Xing Li
XL
Cardiovascular Genetics Laboratory, Eastern Heart Clinic, Center of Thrombosis and Vascular Research, University of New South Wales, Sydney, Australia. xwang@darwin.sfbr.org
Greco
Marissa
M
Sim
Ah Siew
AS
Duarte
Natalia
N
Wang
Jian
J
Wilcken
David E L
DE
D003327:Coronary Disease / Q000209:etiology* / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D012907:Smoking / Q000009:adverse effects*
D019363:Cytochrome P-450 CYP1A1