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Infective endocarditis (IE) is frequently complicated by septic embolism, a need for valve replacement, and death. The development of these complications is associated with the presence, size and mobility of cardiac vegetations, which may form as a result of bacterium-platelet interactions mediated by the platelet glycoprotein GPIb receptor. Variable number tandem repeat (VNTR) and single nucleotide polymorphisms of the gene encoding the GPIb receptor have been described, but their correlation with platelet function, development of vegetations and complications of IE is unknown.The GPIb Kozak T/C, VNTR and human platelet antigen-2a/2b (HPA-2a/2b) genotype of healthy volunteers (n = 156) and patients with IE (n = 35) was determined, and the influence of these polymorphisms on Staphylococcus aureus-induced platelet aggregation in vitro, platelet activation in vivo and clinical outcome in IE was then investigated.The GPIb VNTR C/C genotype was associated with an increased risk of embolism (p = 0.039), with no influence on platelet activation or aggregation, vegetation characteristics or mortality (p0.05 for all). The GPIb Kozak T/C and HPA-2a/2b polymorphisms did not influence the development of complications in patients with IE (all p0.05).The results of these exploratory studies suggest that the GPIb VNTR C/C genotype may predict the development of septic emboli in patients with IE. This hypothesis should be analyzed in larger studies and, if confirmed, would represent an important clinical finding, as it implies that early surgery in patients with the GPIb VNTR C/C genotype could reduce morbidity and mortality in IE.

Cardiac vegetations result from bacterium-platelet adherence, activation and aggregation, and are associated with increased morbidity and mortality in infective endocarditis. The GPIIb/IIIa and FcγRIIa platelet receptors play a central role in platelet adhesion, activation and aggregation induced by endocarditis pathogens such as Staphylococcus aureus, but the influence of known polymorphisms of these receptors on the pathogenesis of infective endocarditis is unknown. We determined the GPIIIa platelet antigen Pl(A1/A2) and FcγRIIa H131R genotype of healthy volunteers (n = 160) and patients with infective endocarditis (n = 40), and investigated the influence of these polymorphisms on clinical outcome in infective endocarditis and S. aureus-platelet interactions in vitro. Platelet receptor genotype did not correlate with development of infective endocarditis, vegetation characteristics on echocardiogram or the composite clinical end-point of embolism, heart failure, need for surgery or mortality (P 0.05 for all), even though patients with the GPIIIa Pl(A1/A1) genotype had increased in vivo platelet activation (P = 0.001). Furthermore, neither GPIIIa Pl(A1/A2) nor FcγRIIa H131R genotype influenced S. aureus-induced platelet adhesion, activation or aggregation in vitro (P 0.05). Taken together, our data suggest that the GPIIIa and FcγRIIa platelet receptor polymorphisms do not influence S. aureus-platelet interactions in vitro or the clinical course of infective endocarditis.