title: Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction.
abstract: BACKGROUND
  Although inherited thrombophilias are more common in patients with venous thromboembolism, their influence on the development of myocardial infarction (MI) requires clarification.
  
  
  RESULTS
  To determine whether there are increased frequencies of mutations/polymorphisms in 14 genes potentially causing thrombophilia in patients with no flow-limiting stenoses after MI compared with patients with > or =1 flow-limiting stenosis of >50%, we studied 395 patients (60 with no flow-limiting stenosis) who underwent angiography at approximately 1 month. The mutations/polymorphisms studied included Factor V Leiden, prothrombin variant G20210A, beta-fibrinogen 448 (G/A), endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate reductase 677 (C/T), platelet glycoprotein IIIa PlA1/A2, plasminogen activator inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282 (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion polymorphism. The frequencies of Factor V Leiden and the beta-fibrinogen 448 A allele were higher in patients with no flow-limiting stenosis than in patients with > or =1 stenosis (11.7% vs 3.6%, odds ratio [OR] 3.6, 95% CI 1.3-9.4, P =.015; and 42% vs 27%, OR 2.0, 95% CI 1.1-3.5, P =.018, respectively), and there was a trend toward an increased frequency of prothrombin variant G20210A (6.7% vs 2.1%, OR 3.4, 95% CI 0.95-11.8, P =.069). However, in patients with no flow-limiting stenosis after MI the frequencies of the other gene mutations/polymorphisms were not increased. Also, there were no significant interactions between any of these 14 mutation/polymorphisms, major cardiovascular risk factors, and the absence of any flow-limiting stenosis, except for Factor V Leiden and hypertension (OR 6.34, 95% CI 2.67-100, P =.004).
  
  
  CONCLUSIONS
  Patients with no flow-limiting stenosis after MI had increased frequencies of 2 inherited thrombophilias (Factor V Leiden and beta-fibrinogen 448 A allele), and there was a trend toward an increased frequency of prothrombin variant G20210A compared with patients with > or =1 stenosis. These data suggest that polymorphisms/mutations in some gene products influencing coagulation may influence the pathogenesis of MI.
authors.affiliation: Department of Molecular Medicine, University of Auckland, Auckland, New Zealand. johnf@adhb.govt.nz
authors.forename: John K
authors.initials: JK
authors.lastname: French
authors.forename: Neil S
authors.initials: NS
authors.lastname: Van de Water
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Sutton
authors.forename: Mayanna
authors.initials: M
authors.lastname: Lund
authors.forename: WanZhen
authors.initials: W
authors.lastname: Gao
authors.forename: Joanne
authors.initials: J
authors.lastname: McDowell
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu-Stratton
authors.forename: Jeanette
authors.initials: J
authors.lastname: Pohorence
authors.forename: Diane
authors.initials: D
authors.lastname: Szymanski
authors.forename: Pascal
authors.initials: P
authors.lastname: Goldschmidt-Clermont
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Browett
authors.forename: Glen
authors.initials: G
authors.lastname: Cooke
mesh_terms: D000328:Adult; D023921:Coronary Stenosis / Q000150:complications / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005340:Fibrinogen