A Polymorphism of a Platelet Glycoprotein Receptor as an Inherited Risk Factor for Coronary Thrombosis

ETHAN J. WEISS, B.A., PAUL F. BRAY, M.D., MATTHEW TAYBACK, Sc.D., STEVEN P. SCHULMAN, M.D., THOMAS S. KICKLER, M.D.,

LEWIS C. BECKER, M.D., JAMES L. WEISS, M.D., GARY GERSTENBLITH, M.D., AND PASCAL J. GOLDSCHMIDT-CLERMONT, M.D.

Abstract

Background: Platelet glycoprotein llb/llla is a membrane receptor for fibrinogen and von Willebrand factor, and it has an important role in platelet aggregation. It is known to be involved in the pathogenesis of acute coronary syndromes. Previously, we found a high frequency of a particular polymorphism, PI^A2, of the gene encoding glyocoprotein llla in kindreds with a high prevalence of premature myocardial infraction.

Methods: To investigate the relation between the PI^A2 polymorphism and acute coronary syndromes, we conducted a case-control study of 71 case patients with myocardial infraction or instable angina and 68 inpatient controls without known heart disease. The groups were matched for age, race, and sex. We used two methods to determine the PI^A genotype: reverse dot blot hybridization and allele-specific restriction digestion.

Results: The prevalence of PI^A2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P=0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of PI^A2 was 50 percent, a value that was 3.6 times that among control subjects under of 60 years of age (13.9 percent, P= 0.002). Among subjects with the PI^A2 polymorphism, the odds ratio was 6.2 (95 percent confidence interval 1.8 to 22.4).

Conclusions: We observed a strong association between the PI^A2 polymorphism of the glyocoprotein llla gene and acute coronary thrombosis, and this association was strongest in patients who had had coronary events before the age of 60 years.

(N Engl J Med 1996; 334:1090-4.)