Gene-Smoking Interaction on Ischemic Stroke: Case-Control Study of Glutathione S-Transferase Polymorphism

Abstract

Background: Smoking is a major risk factor of stroke, but not all smokers develop stroke. This individual difference could be explained by the variation of detoxification capacity. We investigated the relationship of smoking with the genetic polymorphism of a detoxification enzyme (glutathione S-transferase: GST). Methods: This study was conducted as a case-control study. Conventional risk factors for stroke and 3 genetic polymorphisms of GST (GSTM1, GSTT1 , and GSTP1 ) were studied in both 290 acute ischemic stroke patients and 290 age and sex matched controls. Smoking status was determined by urinary cotinine level. The effect of interaction of GST polymorphisms and smoking on stroke risk was investigated. Results: Stroke patients had higher cotinine level compared to that of control (P <0.01). There was little difference between the patient group and control group with regard to the GST polymorphism alone, but significant interaction was noticed between the GST polymorphism and the smoking status. When we stratified the group according to the smoking status by cotinine level, stroke was significantly more frequent in GSTM1 null type and GSTT1, GSTP1 wild type of the high cotinine level group (OR and 95% CI: 2.115,1.219-3.670; 2.620, 1.480-4.638; 2.212, 1.343-3.644 respectively). Conclusion: GST polymorphisms interact with the smoking and confer an increased risk of ischemic stroke, indicating that genetic polymorphism of GST might reveal smokers who are more susceptible to the ischemic stroke.