© 1997 American Heart Association, Inc.
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Plasminogen Activator Inhibitor-1 Promoter 4G/5G Genotype and Plasma Levels in Relation to a History of Myocardial Infarction in Patients Characterized by Coronary Angiography
The Unit of Molecular Vascular Medicine, Research School of Medicine, Leeds, LS1 3EX, UK (N.O.-G., M.W.M., M.H.S., P.J.G.), and the Department of Cardiology, Pinderfields Hospital, Wakefield, UK (N.O.-G., I.J.W.).
Correspondence to N. Ossei-Gerning, University of Leeds, Leeds General Infirmary, Leeds, LSI 3EX, UK.
To investigate the relationship between an insertion/deletion (4G/5G) polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene and the phenotypes of PAI-1 levels, coronary atheroma, and a past history of coronary thrombosis, we studied 453 patients (320 men and 133 women) characterized by coronary angiography. Patients were classified as having normal vessels (n=125) or single-vessel (n=92) or multivessel (n=232) coronary disease on the basis of 
50% stenosis. PAI-1 antigen levels were highest in patients with the 4G/4G genotype (22.5 ng/mL), with a stepwise decrease in levels as the number of 4G alleles decreased (21.5 ng/mL for 4G/5G and 15.8 ng/mL for 5G/5G, P=.02) after adjusting for age, sex, triglyceride levels, and body mass index (BMI). The association between triglyceride level and PAI-1 was genotype specific, with a steeper slope in subjects with the 4G/4G genotype (P=.004). A gene-environment interaction between BMI, PAI-1, and genotype was observed, with a steeper association in patients with the 5G/5G genotype (P=.02). The 4G/4G genotype was significantly associated with a history of myocardial infarction (P<.03; odds ratio, 2.0; 95% CI, 1.1 to 3.7). This relationship was stronger in subjects with diseased vessels (P=.006). There was no relationship between either PAI-1 genotype or levels and the presence of atheroma. Our data suggest that PAI-1 promoter polymorphism influences the development of myocardial infarction through its effect on thrombus formation in patients with preexisting coronary atheroma.
Key Words: plasminogen activator inhibitor-1 • 4G/5G genotype • myocardial infarction • coronary atheroma
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