CYP2A6 gene polymorphism and severity of coronary atherosclerosis in Indonesian male smokers

Nicotine is a toxic alkaloid known to be responsible for the addictive feature of cigarettes. CYP2A6 genetic polymorphism among individuals was suspected to explain the relationship between cigarette smoking and related diseases. CYP2A6 works to slow nicotine metabolism and thus maintain a more prolonged nicotine concentration and increase nicotine exposure to the blood. We aimed to investigate the correlation between the CYP2A6 gene with the severity of coronary atherosclerosis. This cross- sectional study was conducted from April to July 2010 in Makassar Cardiac Centre, Dr Wahidin Sudirohusodo Hospital, Indonesia. Sixty-four male active smokers at the age of ≥45 years, diagnosed with coronary artery disease (CAD), were recruited and asked to smoke the usual number of cigarettes in the last 1 month prior to blood collection for CYP2A6 genotyping. Spearman correlation was performed to analyze the association between the allele variants and coronary stenosis degree, adjusted for CAD risk factors. Furthermore, we estimated the risk ratio to quantify the correlation. Of the 64 male smokers with CAD, the mean duration of smoking was 36.9 ± 8.6 years, and 49 (76.6%) were heavy smokers with >20 cigarettes per day. All 128 alleles were observed. Our results showed that all participants with CYP2A6 variants had a significant correlation with severe coronary artery stenosis (P = .006). Thus, this study suggests that the mutant CYP2A6 gene allele significantly increased the risk of having severe coronary stenosis 1.2 times higher compared to the wild type. This pilot study showed that CYP2A6 gene has an influential role in atherosclerotic development in male smokers. However, our findings should be confirmed with further more extensive studies. Abbreviations: CAD = coronary artery disease, CYP2A6 = cytochrome P450 2A6,FM = fast metabolizers, LAO = left anterior oblique, LCx = left circumflex, Mut = mutant type, PCR-RFLP = polymerase chain reaction-restriction fragment length polymorphism, RAO = right anterior oblique, RR = risk ratio, SD = standard deviation, SM = slow metabolizers, WT = wild type