The GPIIIa P1(A) polymorphism in the progression of abdominal aortic atherosclerosis

Glycoprotein IIIa is expressed in platelets as part of the fibrinogen recep tor and also in vascular endothelium where it mediates smooth muscle cell p roliferation. The association between the glycoprotein GPIIIa P1(A) polymor phism and the stage of atherosclerosis in the abdominal aorta was studied i n a prospective autopsy study series of 300 middle-aged men (33-69 years). The PIA genotype was determined by RFLP-PCR. The stage of atherosclerosis i n the abdominal aorta was determined by computer-assisted morphometry. Elev ated, fibrous lesions were more frequently (P = 0.05) found in the abdomina l aortas of men with the P1(A1) homozygous genotype compared to men with th e A2 allele (OR 2.3; 95% CI 0.99-5.2). The area of complicated lesions was significantly greater in men with P1(A2)-positive genotypes compared to Al homozygotes. The association with complicated lesions was especially strong in men over 60 (P = 0.002). These results suggest that PIA polymorphism is involved in the progression of atherosclerosis in the abdominal aorta. The association of men possessing the p1(A2) allele with slower development of fibrous lesions and with greater area of complicated lesions in the abdomi nal aorta may result from genotypic differences in the smooth muscle cell p roliferation after slight injuries to the endothelium mediated by glycoprot ein IIIa or from genotypic differences in platelet fibrinogen binding or bo th. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.