Glutathione S-transferase gene polymorphism as a susceptibility factor in smoking-related coronary artery disease

Abstract.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world, and cigarette smoking is a major contributing factor to the disease. Glutathione S-transferase (GST) enzyme is implicated in the detoxification of carcinogens present in tobacco smoke and consequent polymorphisms in this gene may confer susceptibility to cardiovascular disease if DNA damage is important in CAD. Therefore, we examined this question in a case-control study of subjects having coronary atheroma by angiography and with a past history of myocardial infarction (MI). The study population consists of 247 healthy controls and 148 consecutive patients who had undergone coronary angiography for suspicion of coronary artery disease. DNA was extracted from whole blood, and the GSTM1 and GSTT1 polymorphisms were determined using a real-time polymerase chain reaction (PCR). We found that the null GSTM1 and GSTT1 genotypes were associated with an increase in the risk of developing coronary heart disease (OR = 1.14; 95% CI: 0.71 – 1.82; OR = 1.38; 95% CI: 0.82 – 2.32), respectively, but this increase was not significant. Patients who smoke having the null genotypes of GSTM1 (OR: 1.63 (1.10 – 2.63)) and GSTT1 (2.66 (1.50 – 4.72)) and both (3.20 (1.37 – 7.45)) were at a higher risk for developing coronary heart disease. In conclusion, the finding of a significant association between GSTM1 and T1 with smoking status may influence cardiovascular disease via DNA damage.