G-33A mutation in the promoter region of thrombomodulin gene and its association with coronary artery disease and plasma soluble thrombomodulin levels

Thrombomodulin is an endothelial glycoprotein that decreases thrombin activ ity and activates protein C. A recent study has shown that G-33A promoter m utation of the thrombomodulin gene occurs particularly in Asians. In this s tudy, we analyzed the distribution of G-33A mutation in the promoter region of the thrombomodulin gene in the Chinese population and determined whethe r the mutation might be a risk far coronary artery disease (CAD). In additi on, the influence of this mutation on plasma soluble thrombomodulin levels in patients with CAD was also examined. We studied 320 consecutive patients (mean age 63 years; 73% men) with CAD and 200 age- and sex-matched control subjects. Screening for thrombomodulin G-33A promoter mutation was conduct ed using polymerase chain reaction, single-strand conformation polymorphism , and direct deoxyribonucleic acid sequencing. The frequency of the G-33A m utation (GA+AA genotypes) was significantly higher in the CAD group (23.8% vs 15.5%, odds ratio [OR] 1.70, p = 0.031). Multiple logistic regression an alysis showed that the mutation was an independent risk factor (OR 1.81, p = 0.016) for CAD, as was hypertension (OR 1.44, p = 0.040), diabetes mellit us (OR 2.50, p < 0.001), and smoking (OR 2.15, p < 0.001). in CAD patients with GG genotype, the soluble thrombomodulin level increased with the exten t of CAD (36 +/- 15 vs 47 +/- 18 vs 55 +/- 36 ng/ml in 1-, 2-, or 3-vessel CAD, p < 0.001). However, in CAD patients with G-33A mutation, there was no difference between the levels of soluble thrombomodulin (39 +/- 17 vs 37 /- 15 vs 42 +/- 18 ng/ml, p = NS) in 1-, 2-, or 3-vessel CAD. Our observati ons suggest that there is a significant association of the G-33A mutation i n thrombomodulin gene with CAD, and this mutation may influence the soluble thrombomodulin levels in patients with CAD. (C) 2000 by Excerpta Medica, I nc.