Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2573-2578
© 1999 American Heart Association, Inc.
Thrombosis |
Glycoprotein IIIa PlA Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly
Abstract—Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocytes, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the PlA1/A2 polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery disease (CAD) is still to be confirmed. Therefore, the association of the PlA polymorphism with the development of coronary atherosclerosis, coronary narrowing, and myocardial infarction (MI) was studied in a prospective, consecutive autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) suffering sudden out-of-hospital or violent death. Coronary atherosclerosis was measured morphometrically and the coronary stenosis percentage determined from a cast rubber model of the coronary tree. We found a significant inverse relation (P=0.01) between the PlA2-positive genotype and coronary artery stenosis. The frequency of possessing the PlA2 allele was significantly (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% stenosis (32.9%). Although the PlA polymorphism was not directly associated with MI, the PlA2 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 47 (12.8%) with MI associated with severe stenosis in the absence of thrombosis. In line with this result, men possessing the PlA2 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 PlA polymorphism is involved in the development of CAD and MI. Men with the PlA2 allele may harbor more thin-walled, vulnerable coronary plaques, plaques prone to rupture, leading to massive, fatal thrombosis. In contrast, men homozygous for the PlA1 allele may more often show stable plaques and present with infarction caused by progressive coronary stenosis.
Key Words: platelet glycoprotein GPIIb/IIIa complex • coronary thrombosis • myocardial infarction • polymorphisms • genetics
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