Effect of the PlA2 alloantigen on the function of β3-integrins in platelets

• Published in: Blood 2001-05, Vol.97 (10), p.3093-3099
• Main Authors: Bennett, Joel S., Catella-Lawson, Francesca, Rut, Andrew R., Vilaire, Gaston, Qi, Weiwei, Kapoor, Shiv C., Murphy, Scott, FitzGerald, Garret A.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.10.3093

The polymorphism responsible for the PlA2 alloantigen on the β3-component of β3-containing integrins is reported to be a risk factor for coronary thrombosis. This study examined the effect of PlA2 on the function of β3-integrins using platelets from subjects homozygous and heterozygous for PlA1 and PlA2. There was overlap in the distribution of the dissociation constant (Kd) and maximum fibrinogen binding (Bmax) values for fibrinogen binding to αIIbβ3 on platelets from PlA1 and PlA2 homozygotes and PlA1/PlA2 heterozygotes. However, whereas there was no statistical difference in these values for the PlA1homozygotes and PlA2 heterozygotes, the Kd for the PlA2 homozygotes was significantly lower than that for the PlA1/PlA2 heterozygotes, but was not statistically different from that for the PlA1 homozygotes. No differences were detected in ADP sensitivity between platelets from PlA1 homozygotes and PlA1/PlA2heterozygotes, in the IC50 for RGDS inhibition of fibrinogen binding to αIIbβ3, in the αvβ3-mediated adhesion of platelets to osteopontin and vitronectin, and in the phorbol ester-stimulated adhesion to fibrinogen of B lymphocytes expressing αIIbβ3 containing either the PlA1 or the PlA2 polymorphism. Finally, no differential effects of PlA2 on turbidometric platelet aggregation, platelet secretion, or platelet thrombus formation were found as measured in the PFA-100. Because no differences were detected in the ability of β3-integrins to interact with ligands based on the presence or absence of the PlA2 polymorphism, the results suggest that factors unrelated to β3-integrin function may account for the reported association of the PlA2 allele with coronary thrombosis.