(Circulation. 1997;95:59-62.)
© 1997 American Heart Association, Inc.
Articles |
Arterial and Venous Thrombosis Is Not Associated With the 4G/5G Polymorphism in the Promoter of the Plasminogen Activator Inhibitor Gene in a Large Cohort of US Men
the Divisions of Cardiovascular Disease (P.M.R., K.L.) and Preventive Medicine (P.M.R., C.H.H.) and the Channing Laboratory (M.J.S.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; the Department of Ambulatory Care and Prevention (C.H.H.), Harvard Medical School; the Department of Cardiology, Children's Hospital, Harvard Medical School (K.L.); and the Departments of Nutrition (M.J.S.), Epidemiology (M.J.S., C.H.H.), and Biological Sciences (K.L.), Harvard School of Public Health, Boston, Mass; and the Division of Laboratory Medicine (J.P.M.), Washington University School of Medicine, St Louis, Mo.
Background The 4G allele of the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor (PAI-1) gene is associated with increased PAI-1 activity. In a small group of young Swedish men, this allele has been reported to predict risk of myocardial infarction. Whether this polymorphism increases risk of arterial and venous thrombosis among middle-aged men is unknown.
Methods and Results Among 14 916 men 40 to 84 years old participating in the Physicians' Health Study who provided baseline blood samples for DNA analysis, 374 suffered first myocardial infarction and 121 had venous thromboembolism during 8.6 years of follow-up. Distributions of the 4G/5G polymorphism in the PAI-1 gene promoter were assessed in these men as well as in a sample of study participants matched on age and smoking who did not develop vascular occlusion during the prospective follow-up period. The distributions of the 4G/4G, 4G/5G, and 5G/5G genotypes among men who developed myocardial infarction (0.27, 0.51, 0.22; P=.7) or venous thromboembolism (0.30, 0.49, 0.21; P=.5) were virtually identical to those of men who remained free of vascular disease (0.27, 0.50, 0.23). Thus, the relative risk of future thrombosis among those with the 4G/4G genotype compared with those without the 4G/4G genotype was 1.02 (95% CI, 0.8 to 1.3). There was no effect modification by age, smoking status, family history of premature thrombosis, history of hypertension, hypercholesterolemia, or aspirin use.
Conclusions These data indicate that the 4G/5G polymorphism in the promoter of the PAI-1 gene is not a major pathogenetic risk factor for arterial or venous thrombosis among middle-aged men.
Key Words: genetics • thrombosis • myocardial infarction • plasminogen activators • risk factors
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