title: Genetic variants associated with rheumatoid arthritis patients and serotypes in European populations.
abstract: OBJECTIVE
  To replicate the association of rheumatoid arthritis (RA) susceptibility loci in an independent European sample and to assess their specificity with anti-citrullinated protein antibodies (ACPA) status.
  
  
  METHODS
  A selection of 64 SNP previously associated with RA have been typed in a cohort of 267 RA patients (169 ACPA-positive and 98 ACPA-negative) and 152 controls from the Rheumatology Units of the University Hospital of Pisa (Italy) and the University of Pécs Medical Center (Hungary). Regression analyses were performed first considering overall RA patients and secondly, taking both serotype subgroups as different disease entities. The results have been adjusted for age, gender and origin of individuals.
  
  
  RESULTS
  The well-known CD2, REL, TNFAIP3, IRF5, PTPRC, and CCR6 have been confirmed as RA disease associated loci together with recently discovered BACH2, RASGRP1, and IKZF3 loci, taking all RA patients as a unique phenotype. Results from both serological subgroups separately reflect the specificity of these susceptibility loci and show additional ACPA-positive specific associations for variants at IL6R, IL2RA, BLK, DDX6, IL6, and TLE3 genes.
  
  
  CONCLUSIONS
  The results from GAPAID project are consistent with previously established RA disease associations for CD2, PTPRC, REL, CCR6, TNFAIP3, IRF5, BLK, IL2RA, and DDX6 loci. In addition, IL6R, BACH2, RASGRP1, TLE3, and IKZF3 are replicated for the first time in an independent European population and IL6 appears to be a suggestive new RA associated locus. The stratified analysis based on ACPA status provides further support for distinct genetic aetiologies of RA subsets, which might have therapeutic implications.
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain. otsanda.ruiz@ehu.eus.
authors.forename: Otsanda
authors.initials: O
authors.lastname: Ruiz-Larrañaga
authors.affiliation: Department of Research and Development, Progenika Biopharma S.A., Derio, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Uribarri
authors.affiliation: Department of Research and Development, Toscana Biomarkers s.r.l., Siena, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Alcaro
authors.affiliation: Department of Research and Development, Progenika Biopharma S.A., Derio, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Escorza-Treviño
authors.affiliation: Department of Research and Development, Progenika Biopharma S.A., Derio, Spain.
authors.forename: Jokin
authors.initials: J
authors.lastname: Del Amo
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Mikel
authors.initials: M
authors.lastname: Iriondo
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Manzano
authors.affiliation: Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.affiliation: Department of Rheumatology and Immunology, University of Pécs, Medical Center, Pécs, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Lóránd
authors.affiliation: Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: Andone
authors.initials: A
authors.lastname: Estonba
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D065288:Serogroup