title: Association study of the platelet collagen receptor glycoprotein VI gene with rheumatoid arthritis.
abstract: OBJECTIVE
  Beyond their role in haemostasis, platelets can actively contribute to immunity. The activation of the platelet collagen receptor glycoprotein VI (GPVI) promotes the release of small extracellular vesicles called microparticles. These microparticles are found in the joint bathing fluid of patients with rheumatoid arthritis (RA) and are thought to amplify inflammation. The gene coding for GPVI is localised on chromosome 19q13.4 and contains different single nucleotide polymorphisms (SNPs). Five non-synonymous SNPs define the major and minor haplotypes of GPVI. The minor haplotype is associated with higher risk of cardiovascular incidents. In this study, we examined whether this minor haplotype is also associated with RA.
  
  
  METHODS
  Allelic discrimination of the SNPs reported to define these haplotypes encoding SKTQH and PEALN protein isoforms, ie rs1613662, rs1654416, rs2304167, rs1654413 and rs1671152, was performed in 399 RA patients and their two parents, all of Western European ethnicity. Statistical analysis relied on the transmission disequilibrium test by the use of the FBAT programme. Haplotypes were also estimated by the FBAT programme.
  
  
  RESULTS
  We observed no statistically significant transmission disequilibrium for the SNPs tested. The major haplotype TAAC, which encodes the SKTQH isoform, was identified in 78% of our cohort individuals, and the CGGA haplotype which encodes the PEALN isoform was identified in 8% of our individuals. We observed no association of these haplotypes of the GPVI gene with RA.
  
  
  CONCLUSIONS
  This demonstrates that the SNPs tested within the GPVI gene are not associated with RA susceptibility and/or severity, suggesting that platelet GPVI may contribute to arthritis independently of its gene polymorphism.
authors.affiliation: Department of Medicine, Faculté de Médecine de l'Université Laval, CHUQ Research center and Division of Rheumatology, CHUQ, Quebec City, QC, Canada. laetitia.michou@crchul.ulaval.ca.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Michou
authors.forename: Francois
authors.initials: F
authors.lastname: Cornélis
authors.forename: Morgane
authors.initials: M
authors.lastname: Baron
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Rene
authors.initials: R
authors.lastname: Westhovens
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Helena
authors.initials: H
authors.lastname: Alves
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
mesh_terms: D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016017:Odds Ratio; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI