title: GPIb VNTR C/C genotype may predict embolic events in infective endocarditis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Cardiovascular ScienceThe Roslin Institute, University of Edinburgh, Chancellor's Building, Edinburgh EH16 4SB, UK. Shruti.X.Daga@gsk.com
authors.forename: Shruti
authors.initials: S
authors.lastname: Daga
authors.forename: James G
authors.initials: JG
authors.lastname: Shepherd
authors.forename: Rachel K Y
authors.initials: RK
authors.lastname: Hung
authors.forename: J Garreth S
authors.initials: JG
authors.lastname: Callaghan
authors.forename: Dana K
authors.initials: DK
authors.lastname: Dawson
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Padfield
authors.forename: J Ross
authors.initials: JR
authors.lastname: Fitzgerald
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
mesh_terms: D000328:Adult; D000368:Aged; D016824:Antigens, Human Platelet / Q000235:genetics; D016022:Case-Control Studies; D004617:Embolism / Q000235:genetics*; D004697:Endocarditis, Bacterial / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*
chemical_list: C115212:2a alloantigen, human; C071221:2b alloantigen, human; D016824:Antigens, Human Platelet; D019038:Platelet Glycoprotein GPIb-IX Complex