title: Association between RANK, RANKL and OPG polymorphisms with ACPA and erosions in rheumatoid arthritis: results from a meta-analysis involving three French cohorts.
abstract: OBJECTIVE
  The RANK/RANKL/osteoprotegerin (OPG) system plays a central role in the pathogenesis of bone erosions in rheumatoid arthritis (RA). The aim of this study was to test the association between 11 single-nucleotide polymorphisms (SNPs) located on RANK, RANKL and OPG genes and anticitrullinated peptide antibody (ACPA) presence or erosions in RA.
  
  
  METHODS
  
  
  
  METHODS
  This work was performed on three independent samples of French patients with RA: the Etude de Suivi des PolyArthrites Indifférenciées Récentes (ESPOIR) (n=632), Rangueil Midi-Pyrénées (RMP) (n=249) and French Rheumatoid Arthritis Genetic Consortium (FRAGC) (n=590) cohorts. Genotyping: the genotyping of 11 SNPs located on RANK, RANKL and OPG were performed by PCR.
  
  
  METHODS
  The association between the genotypes with ACPA or erosions was first tested in the ESPOIR cohort using a χ(2) test and, in the case of significant association, replicated in the RMP and FRACG cohorts. A meta-analysis on the three cohorts was performed using the Mantel-Haenszel method.
  
  
  RESULTS
  One SNP on RANK (rs8086340) and three SNPs on RANKL (rs7984870, rs7325635, rs1054016) were significantly associated with ACPA presence, while one SNP on OPG (rs2073618) and one SNP on RANKL (rs7325635) were significantly associated with erosions in the ESPOIR cohort. Following meta-analysis performed on the three samples, the SNP on RANK and the GGG haplotype of the three SNPs located on RANKL were both significantly associated with ACPA presence, while only the SNP on OPG remained significantly associated with erosions.
  
  
  CONCLUSIONS
  This study identified one SNP located on RANK, one haplotype on RANKL associated with ACPA presence, and one SNP located on OPG associated with erosions in three different samples of French patients with RA.
authors.affiliation: UMR 1027, INSERM, Toulouse, France; University Paul Sabatier Toulouse III, Toulouse, France; Rheumatology Center, Purpan Hospital, Toulouse, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Ruyssen-Witrand
authors.affiliation: University Paul Sabatier Toulouse III, Toulouse, France; Rheumatology Center, Purpan Hospital, Toulouse, France; UMR 1043, INSERM, Toulouse, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Degboé
authors.affiliation: University Paul Sabatier Toulouse III, Toulouse, France; Rheumatology Center, Purpan Hospital, Toulouse, France; UMR 1043, INSERM, Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Cantagrel
authors.affiliation: Rheumatology Center, Purpan Hospital , Toulouse , France.
authors.forename: D
authors.initials: D
authors.lastname: Nigon
authors.affiliation: Rheumatology Department , Lapeyronie Teaching Hospital , Montpellier , France.
authors.forename: C
authors.initials: C
authors.lastname: Lukas
authors.affiliation: UMR 1027, INSERM, Toulouse, France; University Paul Sabatier Toulouse III, Toulouse, France.
authors.forename: S
authors.initials: S
authors.lastname: Scaramuzzino
authors.affiliation: Rheumatology Department , Cochin Teaching Hospital , Paris , France.
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: Department of Rheumatology , Rouen University Hospital & INSERM U905 , Rouen , France.
authors.forename: O
authors.initials: O
authors.lastname: Vittecoq
authors.affiliation: Rheumatology Department , Pellegrin Hospital , Bordeaux , France.
authors.forename: T
authors.initials: T
authors.lastname: Schaeverbeke
authors.affiliation: Rheumatology Department , Lapeyronie Teaching Hospital , Montpellier , France.
authors.forename: J
authors.initials: J
authors.lastname: Morel
authors.affiliation: Department of Rheumatology , Hôpitaux Universitaires de Strasbourg, Université de Strasbourg , Strasbourg , France.
authors.forename: J
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: UMR 1027, INSERM, Toulouse, France; University Paul Sabatier Toulouse III, Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Cambon-Thomsen
authors.affiliation: Rheumatology Department , Claude Bernard-Bichat Teaching Hospital, Paris VII University , Paris , France.
authors.forename: P
authors.initials: P
authors.lastname: Dieudé
authors.affiliation: University Paul Sabatier Toulouse III, Toulouse, France; Rheumatology Center, Purpan Hospital, Toulouse, France; UMR 1043, INSERM, Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Constantin
keywords: Ant-CCP; Gene Polymorphism; Rheumatoid Arthritis