title: Tissue plasminogen activator and risk of myocardial infarction. The Rotterdam Study.
abstract: BACKGROUND
  Impaired fibrinolytic capacity, as assessed by euglobulin clot lysis time or plasma concentration of fibrinolytic parameters, has been associated with an increased risk of myocardial infarction (MI). We studied the association of a polymorphism in the gene for TPA and of plasma concentrations of TPA (antigen and activity) with the prevalence of MI.
  
  
  RESULTS
  A case-control study was performed. Subjects with a history of MI (n = 121) and controls (n = 250) were drawn from the Rotterdam Study, a population-based cohort study of 7983 subjects > or = 55 years old. We determined TPA antigen and activity in plasma and genotyped all subjects for the Alu repeat insertion/deletion polymorphism in intron h in the TPA gene. Homozygosity for the insertion was associated with twice as many cases of MI as was homozygosity for the deletion (odds ratio, 2.24; 95% CI, 1.11-4.50). TPA antigen was positively associated with the risk of MI; compared with that in the lowest quartile, the relative risks (odds ratio) in the second, third, and upper quartiles were 1.7 (CI, 0.9-3.3), 2.3 (1.2-4.4), and 2.0 (1.0-3.8), respectively. When adjusted for body mass index, HDL and total cholesterol, systolic and diastolic blood pressures, and current smoking, the risk associated with TPA antigen concentration was attenuated. Increased concentrations of TPA activity tended to be associated with an increased risk of MI.
  
  
  CONCLUSIONS
  This study provides evidence for an independent association of the insertion allele of the insertion/deletion polymorphism in the TPA gene with nonfatal MI. Increased TPA antigen is associated with an increased risk of MI; however, this association was not independent of cardiovascular disease risk factors.
authors.affiliation: Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: van der Bom
authors.forename: P
authors.initials: P
authors.lastname: de Knijff
authors.forename: F
authors.initials: F
authors.lastname: Haverkate
authors.forename: M L
authors.initials: ML
authors.lastname: Bots
authors.forename: P
authors.initials: P
authors.lastname: Meijer
authors.forename: P T
authors.initials: PT
authors.lastname: de Jong
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: C
authors.initials: C
authors.lastname: Kluft
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004251:DNA Transposable Elements; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007158:Immunologic Techniques; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D010959:Tissue Plasminogen Activator