Pl(A1/A2) polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis

Background The gene encoding the platelet glycoprotein I[la receptor (GPIIIa), shows polymorphism (P-A1/A2. In a previous study, men with acute coronary ischaemia were more likely than controls to carry the P/(A2) allele. This receptor has an important role in acute thrombus formation; these findings therefore raise the possibility of inherited platelet risk factors for both arterial and venous thrombosis. We investigated whether the P/(A2) allele is associated with myocardial infarction, stroke, and Venous thrombosis in a large prospective cohort of men in the USA. Methods 14916 initially healthy men participating in the Physicians' Health Study provided baseline blood specimens for DNA analysis and were followed prospectively for a mean of 8.6 years. 374 men had a first myocardial infarction, 209 stroke, and 121 venous thrombosis during follow-up (704 cases). Distribution of the P/(A1/A2) polymorphism was investigated by a PCR based on restriction-fragment length polymorphism in these men and in a sample of 704 matched study participants who remained free of thrombosis during follow-up (controls). Findings The frequency of the P/(A2) allele was similar to the control frequency (14.8%) among men who had myocardial infarction (13.5%, p=0.4), stroke (13.4%, p=0.5), or Venous thrombosis (14.5%, p=0.9). The relative risk of any Vascular event among men homozygous or heterozygous for P/(A2) compared with men homozygous for P/(A1) was 0.96 (95% CI 0.8-1.2). We found no evidence of association between the P/(A2) allele and myocardia[ infarction (relative risk 0.93 [95 0.7-1.2]), stroke (0.93 [0.7-1.3]), or venous thrombosis (1.07 [0.7-1.6]). There was no evidence of association in subgroup analyses by age, smoking status, and presence of family history of premature coronary disease, hypercholesterolaemia, hypertension, or diabetes. Aspirin use had no effect on these findings. Interpretation In a large cohort of apparently healthy men, carriage of the GPIIIa P/(A2) allele was not associated with any increase in subsequent risk of myocardial infarction, stroke, or Venous thrombosis.