Polymorphisms of cytochrome P450 1A1, cigarette smoking and risk of coronary artery disease.

Epidemiological evidence has demonstrated a strong relationship between cigarette smoking and coronary artery disease (CAD). Cytochrome P450 1A1 (CYP1A1) is a key enzyme that metabolizes the cigarette toxin relevant to smoking-induced atherogenesis. This case-control study examined the role of CYP1A1 polymorphisms, CYP1A1 2A (T6235C) and CYP1A1 2C (A4889G), in susceptibility to smoking-related CAD. We recruited 481 patients with 50% or more luminal obstructions in the coronary artery and 228 normal subjects at a medical center in Taiwan. Information on socio-demographic and smoking status was obtained using a self-administered questionnaire. Genotypes of CYP1A1 2A and CYP1A1 2C polymorphisms were determined by polymerase chain reaction or in combination with restriction fragment length polymorphism methods. The results did not show any significant association between CYP1A1 2A polymorphism and CAD risk. However, the CYP1A1 2C G allele was more prevalent in controls (p=0.035) with a dose-response protective effect for CAD. Compared to the A/A genotype, the multivariate logistic regression analysis showed that carrying the CYP1A1 2C G/G genotype was associated with a significantly decreased risk for CAD (OR=0.32, 95% CI=0.15-0.70). The beneficial effect of the CYP1A1 2C G/G genotype was even greater for never smokers than those carrying the A/A genotype (OR=0.23, 95% CI=0.08-0.71). The interaction between genotype and smoking status was not statistically significant. Our findings suggest that the CYP1A1 2C G/G genotype may reduce the risk for CAD in the Taiwanese population and this effect appeared to be more pronounced among never smokers.