Membrane glycoprotein (GP) IIb/IIIa plays a major role in platelet function; indeed it enables stimulated platelets to bind fibrinogen and related adhesive proteins, a process that is considered key in the development of thrombosis. The gene encoding GPIIIa (ITGB3, also known as GP3A) shows a common platelet antigen polymorphism [PL(A1)/PL(A2); expressed by alleles ITGB3*001 and ITGB3*002] that was variably associated with vascular disease. In 1996, the presence of the PL(A2) allele (ITGB3*001) was first reported to increase the risk of coronary heart disease. Shortly after, the interest in this study was increased by the publication of a case report on the death from myocardial infarction of an Olympic athlete who was found to be homozygous for the PL(A2) allele. Overviews of the published studies on the PL(A1)/PL(A2) polymorphism and coronary risk suggest an influence of the PL(A2) allele on the clinical phenotype and the interaction with other environmental factors. In particular, the strongest effect of the ITGB3 PL(A2) allele was expressed on the risk of occlusion after revascularization procedures, mainly after stent implantation, a condition in which platelet activation is more important as compared with other stenotic mechanisms.
In the future, the identification of patients who are particularly responsive to GPIIb/IIIa antagonist therapy (e.g. those with the PL(A2) allele) might help to improve the treatment efficacy in this relatively small population. In a mechanism possibly unrelated to its effect on platelet reactivity to aggregating stimuli, the presence of the PL(A2) allele might influence the antiaggregatory effect of platelet inhibitory drugs such as aspirin (acetylsalicylic acid), clopidogrel, and GPIIb/IIIa antagonists.
Although interesting, current data does not yet have direct clinical implications for patient risk identification and drug therapy tailoring. Larger studies are necessary to define the role of the PL(A2) allele in more homogeneous groups where platelet GPIIb/IIIa activation might be particularly relevant.
Coronary Artery Disease Aspirin Platelet Function Abciximab Platelet Reactivity
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This work was supported by a grant from the Italian Ministry of Health, Rome, Italy (contract no. 211 RF 2002) and by the EU project IMMIDIET QLK1-CT-2000-00100.
The authors have no conflicts of interest that are directly relevant to the content of this review.
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