GENE POLYMORPHISMS FOR PAI-1 ARE ASSOCIATED WITH THE ANGIOGRAPHIC EXTENT OF CORONARY-ARTERY DISEASE

Localized regulation of fibrinolytic protein gene expression is associ ated with the histologic extent of atherosclerosis. This regulation ma y be dependent on the presence of certain fibrinolytic protein gene po lymorphisms. The relationship between the plasminogen activator inhibi tor (PAI)-1 HindIII and the tissue plasminogen activator (t-PA) EcoR1 gene polymorphisms and the extent of coronary artery disease (CAD) wer e investigated in 49 Caucasian patients with symptomatic CAD. There wa s a strong association between PAI-1, but not t-PA, gene polymorphisms and the extent of CAD detected by coronary angiography. Patients homo zygous for the presence or absence of the PAI-1 HindIII (1/1, 2/2 PAI- 1) gene polymorphisms had a significantly greater extent of CAD (numbe r of diseased vessels) than patients with the respective heterozygous forms (vs. 1/2 PAI-1, P = 0.05). Stepwise ordinal multiple regression analysis of classic CAD risk factors and fibrinolytic protein genotype s indicated that only the PAI-1 genotypes were predictive of the exten t of angiographic CAD (P = 0.019). Analysis of variance between classi c risk factors and fibrinolytic protein genotypes identified an associ ation between t-PA genotypes and a history of prior infarction or stro ke. Fibrinolytic gene polymorphisms for PAI-1 are associated with the extent of CAD in symptomatic patients and with certain risk factors fo r coronary atherosclerosis.