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/

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 acros s all centres but in controls, levels in the French centres were signi ficantly higher. Only in Belfast were PAI-1 levels higher in cases (11 .7 AU/ml) than controls (10.5 AU/ml). The PAI-1 4G allele frequency wa s similar in cases and controls (0.55 and 0.54). In all groups, 4G hom ozygotes had the highest mean plasma PAI-1 level (4G4G vs 5G5G; cases overall: 14.2 vs 12.1 AU/ml; controls overall: 15.0 vs 12.6 AU/ml), wi th 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 f actor for MI but is associated with PAI-1 activity. Thus homozygosity for the 4G allele may predispose to elevated PAI-1 and impaired fibrin olysis, perhaps requiring interaction with other genetic or environmen tal factors to influence MI risk.