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

Glycoprotein IIIa is expressed in platelets as part of the fibrinogen receptor and also in vascular endothelium where it mediates smooth muscle cell proliferation. The association between the glycoprotein GPIIIa Pl(A) polymorphism and the stage of atherosclerosis in the abdominal aorta was studied in a prospective autopsy study series of 300 middle-aged men (33-69 years). The Pl(A) genotype was determined by RFLP-PCR. The stage of atherosclerosis in the abdominal aorta was determined by computer-assisted morphometry. Elevated, fibrous lesions were more frequently (P=0.05) found in the abdominal aortas of men with the Pl(A1) homozygous genotype compared to men with the A2 allele (OR 2.3; 95% CI 0.99-5.2). The area of complicated lesions was significantly greater in men with Pl(A2)-positive genotypes compared to A1 homozygotes. The association with complicated lesions was especially strong in men over 60 (P=0.002). These results suggest that Pl(A) polymorphism is involved in the progression of atherosclerosis in the abdominal aorta. The association of men possessing the Pl(A2) allele with slower development of fibrous lesions and with greater area of complicated lesions in the abdominal aorta may result from genotypic differences in the smooth muscle cell proliferation after slight injuries to the endothelium mediated by glycoprotein IIIa or from genotypic differences in platelet fibrinogen binding or both.