title: Thrombomodulin gene mutations associated with myocardial infarction.
abstract: 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.
  
  
  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 transcription control elements within the thrombomodulin gene. In contrast, no difference was observed between patients and control subjects for the allelic frequency of a previously identified neutral polymorphism GCC/GTC coding for Ala/Val455, with 3 individuals homozygous for GTC (Val) in both groups.
  
  
  CONCLUSIONS
  The findings suggest that mutations in the promoter region of the thrombomodulin gene may constitute a risk for arterial thrombosis.
authors.affiliation: Department of Haematology, Charing Cross and Westminster Medical School, London, UK. h.ireland@cxwms.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Ireland
authors.forename: G
authors.initials: G
authors.lastname: Kunz
authors.forename: K
authors.initials: K
authors.lastname: Kyriakoulis
authors.forename: P J
authors.initials: PJ
authors.lastname: Stubbs
authors.forename: D A
authors.initials: DA
authors.lastname: Lane
mesh_terms: D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018570:Risk Assessment; D018180:Thrombomodulin / Q000235:genetics*
chemical_list: D018180:Thrombomodulin