Glycoprotein IIIa Pl(A) polymorphism associates with progression of coronary artery disease and with myocardial infarction in an autopsy series of middle-aged men who died suddenly

Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocyte s, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the Pl(A1/A2) polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery diseas e (CAD) is still to be confirmed. Therefore, the association of the PIA pol ymorphism with the development of coronary atherosclerosis, coronary narrow ing, and myocardial infarction (MI) was studied in a prospective, consecuti ve autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) su ffering sudden out-of-hospital or violent death. Coronary atherosclerosis w as measured morphometrically and the coronary stenosis percentage determine d from a cast rubber model of the coronary tree. We found a significant inv erse relation (P=0.01) between the Pl(A2)-positive genotype and coronary ar tery stenosis. The frequency of possessing the Pl(A2) allele was significan tly (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.22 to 0.98) lower among men with >50% coronary stenosis (18.3%) than among those with <25% s tenosis (32.9%). Although the Pl(A) polymorphism was not directly associate d with MI, the Pl(A2) allele was present in 11 of the 22 men (50%) with MI and coronary thrombosis (OR 6.6, 95% CI 2.1 to 22.8) but in only 6 of the 4 7 (12.8%) with MI associated with severe stenosis in the absence of thrombo sis. In Line with this result, men possessing the Pl(A2) allele also had a larger area of fissured and ulcerated complicated lesions in their coronary arteries (P<0.05). The present results suggest that the Pl(A) polymorphism is involved in the development of CAD and MI. Men with the Pl(A2) allele m ay harbor more thin-walled, vulnerable coronary plaques, plaques prone to r upture, leading to massive, fatal thrombosis. In contrast, men homozygous f or the Pl(A1) allele may more often show stable plaques and present with in farction caused by progressive coronary stenosis.