ARTERIAL AND VENOUS THROMBOSIS IS NOT ASSOCIATED WITH THE 4G 5G POLYMORPHISM IN THE PROMOTER OF THE PLASMINOGEN-ACTIVATOR INHIBITOR GENE INA LARGE COHORT OF US MEN/

Background The 4G allele of the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor (PAI-1) gene is associated with in creased PAI-1 activity. In a small group of young Swedish men, this al lele has been reported to predict risk of myocardial infarction. Wheth er 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 m yocardial infarction and 121 had venous thromboembolism during 8.6 yea rs 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 stu dy participants matched on age and smoking who did not develop vascula r occlusion during the prospective follow-up period. The distributions of the 4G/4G, 4G/5G, and 5G/5G genotypes among men who developed myoc ardial 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 r emained free of vascular disease (0.27, 0.50, 0.23). Thus, the relativ e risk of future thrombosis among those with the 4G/4G genotype compar ed 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 hist ory of premature thrombosis, history of hypertension, hypercholesterol emia, or aspirin use. Conclusions These data indicate that the 4G/5G p olymerphism in the promoter of the PAI-1 gene is not a major pathogene tic risk factor for arterial or venous thrombosis among middle-aged me n.