title: The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I'nfarctus du Mycocarde.
abstract: We have investigated the interrelationships of plasma PAI-1 activity, the PAI-1 4G/5G polymorphism and risk of myocardial infarction (MI) in the ECTIM study, a case-control study of MI based in Belfast, Lille, Strasbourg and Toulouse. Mean PAI-1 levels in cases were similar across all centres but in controls, levels in the French centres were significantly higher. Only in Belfast were PAIl1 levels higher in cases (11.7 AU/ml) than controls (10.5 AU/ml). The PAI-1 4G allele frequency was similar in cases and controls (0.55 and 0.54). In all groups, 4G homozygotes had the highest mean plasma PAI-1 level (4G4G vs 5G5G; cases overall: 14.2 vs 12.1AU/ml; controls overall: 15.0 vs 12.6AU/ml), with the heterozygotes generally intermediate. The data from Belfast are consistent with the literature implicating PAI-1 level as an MI risk factor. In ECTIM, the PAI-1 4G/5G polymorphism is not a genetic risk factor for MI but is associated with PAI-1 activity. Thus homozygosity for the 4G allele may predispose to elevated PAI-1 and impaired fibrinolysis, perhaps requiring interaction with other genetic or environmental factors to influence MI risk.
authors.affiliation: Department of Medicine, University College London Medical School, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ye
authors.forename: F R
authors.initials: FR
authors.lastname: Green
authors.forename: P Y
authors.initials: PY
authors.lastname: Scarabin
authors.forename: V
authors.initials: V
authors.lastname: Nicaud
authors.forename: L
authors.initials: L
authors.lastname: Bara
authors.forename: S J
authors.initials: SJ
authors.lastname: Dawson
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: G
authors.initials: G
authors.lastname: Luc
authors.forename: J P
authors.initials: JP
authors.lastname: Cambou
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D005602:France / Q000453:epidemiology; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D009660:Northern Ireland / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014944:World Health Organization
chemical_list: D017395:Plasminogen Activator Inhibitor 1