title: Genetic variation in the human thrombomodulin promoter locus and prognosis after acute coronary syndrome.
abstract: BACKGROUND
  Endothelial thrombomodulin (TM) plays a critical role in both anticoagulation and anti-inflammation. An impaired TM cofactor function or reduced TM gene expression could constitute a prethrombotic abnormality leading to acute coronary events. Mutations in the TM gene occur, but their functional consequences on the expression and activity of the gene are not yet fully understood.
  
  
  METHODS
  We performed a prospective study investigating the prevalence of TM mutations in the promoter region in 182 patients with acute coronary syndrome as well as in a control group. The patients were followed-up after 30 days and after 2 years for acute myocardial infarction (MI) and mortality.
  
  
  CONCLUSIONS
  We identified 10 point mutations and 2 small deletions: -1861 C/A, -1852 C/G, -1803 G/C, -1752 G/C, -1213/1212 delTT, -1089 C/G, -1088 C/T, -1083/1082 delCC, -1066 A/C, -801 C/G, -651 A/C and -52 G/A. Two of the mutations, -1752 G/C and -1213/1212 delTT, were frequent in the patients as well as in the controls, while all the others were rare. The only significant finding was that both -1752 G/C and -1213/1212 delTT were associated with a lower than normal risk of suffering a clinical event among smokers at 30 days and 2 years. We did not gain any support for the hypothesis that TM mutations confer an increased risk of MI or mortality.
authors.affiliation: Institute of Laboratory Medicine, Department of Clinical Chemistry, Lund University Hospital, Lund University, Sweden. Ann-Kristin.Ohlin@klinkem.lu.se
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Ohlin
authors.forename: Johan
authors.initials: J
authors.lastname: Holm
authors.forename: Andreas
authors.initials: A
authors.lastname: Hillarp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics* / Q000401:mortality; D004247:DNA / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000401:mortality; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D017384:Sequence Deletion; D016019:Survival Analysis; D018180:Thrombomodulin / Q000235:genetics*
chemical_list: D018180:Thrombomodulin; D004247:DNA