ALU-REPEAT POLYMORPHISM IN THE GENE CODING FOR TISSUE-TYPE PLASMINOGEN-ACTIVATOR (T-PA) AND RISKS OF MYOCARDIAL-INFARCTION AMONG MIDDLE-AGED MEN

An Alu-repeat polymorphism in the gene coding for tissue-type plasmino gen activator has been described recently, and it has been hypothesize d that this polymorphism may predict risk of coronary thrombosis. In a prospective cohort of nearly 15,000 apparently healthy men, presence of an Alu-repeat insertion/deletion (I/D) polymorphism in the gene cod ing for tissue-type plasminogen activator was determined among 369 stu dy participants who subsequently suffered a first myocardial infarctio n (cases) and among a group of 369 age- and smoking-matched study part icipants who remained free of reported cardiovascular disease during f ollow-up (controls). The distributions of the II, DI, and DD genotypes of the tissue-type plasminogen activator polymorphism among men who s ubsequently suffered myocardial infarction (0.30, 0.50, 0.21) were vir tually identical to those who remained free of disease (0.29, 0.50, 0. 21; P=.9). There was no evidence of association between the Aim insert ion polymorphism and risks of future myocardial infarction in models a ssuming either allelic recessive (relative risk, 1.05; 95% confidence interval, 0.8 to 1.4, P=.8) or allelic dominant (relative risk, 1.04; 95% confidence interval, 0.7 to 1.5, P=.8) modes of inheritance, nor w ere associations found in analyses stratified by age, family history, hypercholesterolemia, or the presence of other risk factors for premat ure coronary disease. Multivariate analysis had no important effects o n these relationships. In this cohort of middle-aged US men, the prese nce of the insertion allele of the Alu-repeat polymorphism of the tiss ue-type plasminogen activator gene is not associated with future risks of myocardial infarction.