title: The minor allele of GP6 T13254C is associated with decreased platelet activation and a reduced risk of recurrent cardiovascular events and mortality: results from the SMILE-Platelets project.
abstract: BACKGROUND
  Contradictory results have been published on the effects of T13254C (rs1613662), which distinguishes the two major isoforms of GP6, the gene encoding the platelet receptor glycoprotein VI, on platelet function and the risk of cardiovascular disease.
  
  
  METHODS
  We performed a population-based case-control study, the Study of Myocardial Infarctions in Leiden, among 547 male patients with a first myocardial infarction (MI) and 646 control subjects, as well as a prospective cohort study in which the same MI patients were followed for recurrent events (fatal and non-fatal MI and unstable angina) and mortality (median follow-up of 12 years). P-selectin expression by platelets induced by crosslinked collagen-related peptide (CRP-XL) was measured by whole blood flow cytometry in 274 MI patients.
  
  
  RESULTS
  T13254C was not associated with a first MI, but seemed to be associated with a reduced incidence of recurrent events [per-allele hazard ratio 0.77, 95% confidence interval (CI) 0.56-1.06] and mortality (hazard ratio 0.57, 95% CI 0.37-0.89). Pooling with the Heart and Estrogen/Progestin Replacement Study revealed hazard ratios of 0.81 (95% CI 0.66-0.99) and 0.73 (95% CI 0.55-0.96). The minor C-allele was also strongly associated with a reduced percentage of P-selectin-expressing platelets. The reduction per C-allele was 23% (95% CI 18-28%). In an independent study of 219 healthy volunteers, the per-allele reduction of CRP-XL-induced aggregation was 10% (95% CI 2-18%).
  
  
  CONCLUSIONS
  The minor allele of GP6 T13254C that reduced platelet activation and aggregation also seemed to be associated with a reduced incidence of recurrent cardiovascular events and mortality, but was not associated with first MI.
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: J D
authors: JD
authors: Snoep
authors: P
authors: P
authors: Gaussem
authors: J C J
authors: JC
authors: Eikenboom
authors: J
authors: J
authors: Emmerich
authors: J J
authors: JJ
authors: Zwaginga
authors: C E
authors: CE
authors: Holmes
authors: H L
authors: HL
authors: Vos
authors: Ph G
authors: PG
authors: de Groot
authors: D M
authors: DM
authors: Herrington
authors: P F
authors: PF
authors: Bray
authors: F R
authors: FR
authors: Rosendaal
authors: J G
authors: JG
authors: van der Bom
mesh_terms: D000368:Aged; D000483:Alleles; D001792:Blood Platelets / Q000166:cytology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000235:genetics*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D020033:Protein Isoforms; D012008:Recurrence
chemical_list: D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D020033:Protein Isoforms; C098341:platelet membrane glycoprotein VI