Effect Of Thrombomodulin Gene Promoter G-33A Polymorphism On The Onset Of Acute Myocardial Infarction

Objective Occlucive thrombus formation at the site of a raptured atherosclerotic plaque in coronary artery is the most important pathologic basis of acute myocardial infarction(AMI). There is an increased awareness of the contribution of inherited hemostatic disorders as risks for coronary thrombosis. Thrombomodulin is an endothelial cell surface glycoprotein receptor for thrombin. It plays an important role in the regulation of blood coagulation by converting thrombin from a procoagulant to a physiological anticoagulant factor. We performed a case-control study to investigate the effect of thrombomodulin gene promoter G-33A polymorphism on the onset of acute myocardial infarction.Methods 177 cases with AMI and 200 controls were recruited to participate the study. Polymerase chain reaction and single strand conformation polymorphism was used to define the thrombomodulin gene promoter G-33A polymorphism. Conventional risk factors of AMI such as smoking, drinking, hypertension, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and familial history of thromboembolic diseases were also measured.Results (1) The frequency of thrombomodulin GA+AA genotype among patients with AMI was significantly higher than that among control subjects ( 21.47% vs 12.50%, x2=5.427, P=0.020, OR1.914, 95%CI 1.102-3.323). (2) According to the age of the patients with first attacks, the AMI group was divided into two subgroups: A group ( 45 years old ) and B group ( >45 years old). The frequency of thrombomodulin GA+AA genotype were significantly higher in A group than those in B group (31.37% vs 17.46%, x2=4.168, P=0.041). (3) There was no significant difference between male and female AMI patients (24.41% vs 14.00%,x 2=2.306, P=0.129). (4) Smoking, hypertension, hypercholesterolemia, and thrombomodulin promoter G-33A polymorphism were the independent risk factors for AMI. (5) Smoking and familial history of thromboembolic diseases were significantly corelated to thrombomodulin gene promoter G-33A polymorphism. ()6 There is a gene-environment interaction between smoking and thrombomodulin promoter G-33A polymorphism on the onset of AMI. The clinical effect of this genetic factor was enhanced by smoking.Conclusion ()1We concluded that there was a significant association between the thrombomodulin promoter G-33A polymorphism and AMI in our population, especially in young patients( 45 years old). The carriers of GA+AA genotype have genetic susceptibility to AMI. (2)Smoking and familial history of thromboembolic diseases were significantly corelated to thrombomodulin gene promoter G-33A polymorphism. (3) There is a gene-environment interaction between smoking and thrombomodulin promoter G-33A polymorphism on the onset of AMI. Like other genetic risk factors, thrombomodulin gene promoter G-33A polymorphism just makes the carriers have genetic susceptibility to AMI, whether they have AMI or not will depend on the interaction between genes and the environment.