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.

Glutathione S-transferase mu1 deficiency, cigarette smoking and coronary artery disease.

BACKGROUND: While genetic variation accounts for a large proportion of interindividual differences in coronary artery disease (CAD) development, environmental factors such as cigarette smoking may genotype-dependently initiate or accelerate the risk. Glutathione S-transferase mu1 (GSTM1) is one of the GST isoenzymes and contributes to the detoxification process of organic compounds produced by cigarette smoking. In the present study we explored the hypothesis that GSTM1 deficiency, caused by GSTM1 null allele, may predispose subjects to cigarette smoking related CAD risk. DESIGN: Cross-sectional. METHODS: We genotyped the GSTM1 null allele in 868 angiographically characterized CAD patients who were consecutively recruited in the present study. RESULTS: The frequency of the null genotype in this high-risk patient population was 57.1% (55.4% for males and 61.0% for females). While 75.7% male and 50.7% female null GSTM1 patients had significant CAD as defined by one or more significantly stenosed coronary arteries, 79.3% male and 48.3% female patients with positive GSTM1 also had the significant CAD (P > 0.05). However, although 54.3% male and 55.2% female GSTM1 null patients had triple vessel disease, only 45.7% male and 44.5% female GSTM1 positive patients had the severe disease. Controlling for cigarette smoking did not change the relationship. The occurrences of MI were 37.9% in male and 31.4% in female with the null genotype whereas they were 42.8% in male 37.6% in female with positive GSTM1 (P > 0.05). Using logistic regression analyses, we found no interactions between GSTM1 genotype and cigarette smoking in relation to CAD or MI. CONCLUSIONS: While our data may be consistent with that the GSTM1 null genotype predisposes subjects to cigarette smoking related severe CAD, interactive effect on CAD risk is minor and insignificant. GSTM1 deficiency alone is not sufficient to cause CAD.