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.

Genetic polymorphisms influence runners’ responses to the dietary ingestion of antioxidant supplementation based on pequi oil (Caryocar brasiliense Camb.): a before-after study

“…Because GST M1 and T1 null genotypes result in a complete absence of activity in their respective enzymes [52,68], these common deletion polymorphisms have been widely investigated for their effect on the risk of myocardial infarction [142], hypertension [80,103], and smoking-related and nonrelated coronary artery disease (CAD); [1,50,54,84,130,140]. However, these studies have yielded contradictory results, with some studies showing a significant association, and others showing no such association [140].…”

A physiogenomic approach to study the regulation of blood pressure

“…The Atherosclerosis Risk in Communities study demonstrated that Gtsm1 polymorphisms modify the effect of smoking on endothelial function and atherosclerosis (25). Thus smokers having the null genotype of GSTM1 are at a higher risk for developing coronary heart disease (36). ROS induce glutathione S-transferases by antioxidant response elements (16).…”

The frequency of GSTT1 null genotype in Turkish population and lung cancer risk

“…[26], [27] In our study with Turkish population subjects, the incidence of GSTT1 deletion in healthy controls was significantly lower (10.8%) compared to those of other studies (17.3-28.3%) in Turkish population. [28][29][30][31][32][33][34] Overall, the GSTT1 null genotype was found to be higher (25.4%) among the Turkish populations as compared to European but lower than Singapore, Japan, and Korea. [35] We can conclude that carrying the GSTT1 null genotype may be accepted as a weak risk factor for the susceptibility to lung cancer.…”