GPIb VNTR C/C genotype may predict embolic events in infective endocarditis

Shruti Daga, James G Shepherd, Rachel K Y Hung, J Garreth S Callaghan, Dana K Dawson, Gareth J Padfield, J Ross Fitzgerald, David E Newby

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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 (p > 0.05 for all). The GPIb Kozak T/C and HPA-2a/2b polymorphisms did not influence the development of complications in patients with IE (all p > 0.05).
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.
Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalThe Journal of heart valve disease
Issue number1
Publication statusPublished - Jan 2013


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