89. Polymorphism of the blood clot lysis enzyme tissue-type plasminogen activator is associated with myocardial infarction

Objective: Impaired fibrinolysis has been suggested to be associated with increased risk of myocardial infarction. An insertion/deletion (I/D) polymorphism of the tissue-type plasminogen activator (t-PA) gene has been described which may be associated with impaired fibrinolysis. We studied the association between this polymorphism and the prevalence of myocardial infarction. Design: A population based case control study. Setting: A district of Rotterdam, the Netherlands. Participants: From the cohort that consisted of 7983 men and women aged 55 years and over, we selected 162 subjects with a documented history of myocardial infarction and 258 age matched control subjects without arterial disease. Measurements: All subjects were typed for the Alu sequence insertion/deletion polymorphism located in intron h of the t-PA gene. Results: Allele frequencies were 0.54 for the insertion allele and 0.46 for the deletion allele, and were in Hardy Weinberg equilibrium. Homozygosity for the insertion (n=138) was associated with an increased risk of myocardial infarction compared to homozygosity (n=75) for the deletion: relative risk 2.0(95% CI 1.1, 3.6). Conclusion: These findings suggest an association of the insertion allele of the t-PA gene with the occurrence of myocardial infarction. The I/D polymorphism seems to be a linkage marker for an unknown mutation at, or near, the tPA gene. The insertion allele may reflect an impaired capacity of the fibrinolytic system to respond adequately to acute coronary thrombosis.