Thrombomodulin Gene Mutations Associated With Myocardial Infarction

Background Thrombomodulin is an important receptor for thrombin on the endothelial cell surface of most blood vessels, including those of the heart. Thrombin-bound thrombomodulin activates protein C, which inhibits thrombin generation by degrading factors Va and VIIIa. The aim of this study was to analyze the 5′ region of the thrombomodulin gene to determine whether mutations contribute a risk for myocardial infarction. Methods and Results We screened the promoter region of the thrombomodulin gene by single-stranded conformation polymorphism analysis in 104 patients with diagnosed myocardial infarction. Five mutations (three distinct) were identified (GG−9/−10AT, G−33A, and C−133A). The dinucleotide mutation GG−9/−10AT was identified in 3 individuals (2 heterozygous, 1 homozygous). Only one of the three different mutations was identified in 104 patient control subjects matched for age, sex, and race (G−33A in a single individual). All mutations identified were in close proximity to consensus sequences for...