Platelet Pl(A2) allele and incidence of coronary heart disease: Results from the atherosclerosis risk in communities (ARIC) study

Background - The major platelet integrin glycoprotein IIb-IIIa plays a primary role in platelet aggregation and acute thrombus formation at the site of vascular injury. A genetic polymorphism of glycoprotein IIb-IIIa (Pl(A)) has recently been proposed as a potential genetic factor linking to platelet hyperaggregability and increased risk of myocardial infarction. Despite numerous, mostly nonprospective studies, the role of this polymorphism as a clinically relevant, inherited risk factor for coronary heart disease (CHD) is still controversial. The purpose of this study was to determine whether Pl(A2) is a risk factor for incident CHD and whether it is correlated with increased platelet activation in a case-cohort study nested within a prospective epidemiologic investigation. Methods and Results - Blood samples were collected and processed from the Atherosclerosis Risk in Communities Study cohort at the baseline examination (1987 to 1989). They were stored at -80°C. Pl(A1/A2) genotype and plasma β-thromboglobulin levels were determined in 439 incident CHD cases and a reference cohort sample of 544 (of whom 18 were also CHD cases). The prevalence of the Pl(A2) allele was not different in cases versus noncases. No significant correlation between CHD risk factors and the Pl(A2) allele was noted either. Platelet activation, as measured by plasma β-thromboglobulin levels, was not enhanced in individuals with the Pl(A2) allele. Conclusions - This prospective study indicates that healthy individuals carrying the Pl(A2) allele do not have an increased risk of CHD.