The
GPIIIa (
beta3 integrin) is an integral part of two
glycoprotein receptors - the
GP(IIb/IIIa)
fibrinogen receptors in platelets and the GP(V/IIIa)
vitronectin receptors in endothelium and vascular smooth muscle cells (vSMC). The PlA polymorphism of the gene for
GPIIIa (
beta3 integrin) has been suggested to play an important role in the progression of
coronary artery disease (CAD) and in
coronary thrombosis. Whether the action of the PlA polymorphism is due to differences in platelet aggregability or function of the vSMC and endothelial
GPIIIa is not known. The association of the PlA polymorphism with the early, non-complicated
atherosclerosis and CAD was studied in the Helsinki
Sudden Death Study (HSDS) comprising two independent, autopsy series of altogether 700 middle-aged Caucasian Finnish men (33-70 year) suffering sudden out-of-hospital death. The burden of complicated lesions was greater in men with the A2 allele (heterozygotes or homozygotes for A2) (P=0.01) compared with PlA1/A1 homozygotes in the entire series. To further estimate the role of platelet-independent
GPIIIa receptors, we excluded all cases with
coronary thrombosis and
thrombus-overlaid complicated lesions. In this subset of men, fibrous coronary lesions were more frequent (OR 2.9; P<0.01) in the coronary arteries of PlA1/A1 homozygotes compared with men with the PlA2 allele. Moreover, men with the PlA1/A1 genotype also had more stenotic coronary arteries (P<0.05) compared with men with the A2 allele at this early, non-complicated stage of
atherosclerosis. The findings of this study suggest that Pl(A1/A1) homozygotes may be prone to early
atherosclerosis and more rapid progression of stable CAD whereas carriers of the PlA2 allele are more prone to thrombotic complications. We hypothesize that the PlA polymorphism may account for the early
atherosclerosis by affecting the function of endothelial and vSMC GP(V/IIIa) receptors, whereas the PlA polymorphism on platelet
GP(IIb/IIIa) receptors may play a major role in
coronary thrombosis.