title: Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility.
abstract: BACKGROUND
  Genome-wide association studies of rheumatoid arthritis (RA) have identified an association of the disease with a 6q23 region devoid of genes. TNFAIP3, an RA candidate gene, flanks this region, and polymorphisms in both the TNFAIP3 gene and the intergenic region are associated with systemic lupus erythematosus. We hypothesized that there is a similar association with RA, including polymorphisms in TNFAIP3 and the intergenic region.
  
  
  METHODS
  To test this hypothesis, we selected tag-single nucleotide polymorphisms (SNPs) in both loci. They were analyzed in 1,651 patients with RA and 1,619 control individuals of Spanish ancestry.
  
  
  RESULTS
  Weak evidence of association was found both in the 6q23 intergenic region and in the TNFAIP3 locus. The rs582757 SNP and a common haplotype in the TNFAIP3 locus exhibited association with RA. In the intergenic region, two SNPs were associated, namely rs609438 and rs13207033. The latter was only associated in patients with anti-citrullinated peptide antibodies. Overall, statistical association was best explained by the interdependent contribution of SNPs from the two loci TNFAIP3 and the 6q23 intergenic region.
  
  
  CONCLUSIONS
  Our data are consistent with the hypothesis that several RA genetic factors exist in the 6q23 region, including polymorphisms in the TNFAIP3 gene, like that previously described for systemic lupus erythematosus.
authors.affiliation: Laboratorio de Investigacion 2 and Rheumatology Unit, Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. rebeca.dieguez@usc.es
authors.forename: Rebeca
authors.initials: R
authors.lastname: Dieguez-Gonzalez
authors.forename: Manuel
authors.initials: M
authors.lastname: Calaza
authors.forename: Eva
authors.initials: E
authors.lastname: Perez-Pampin
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
authors.forename: Rafael
authors.initials: R
authors.lastname: Caliz
authors.forename: Luis
authors.initials: L
authors.lastname: Carreño
authors.forename: Arturo R
authors.initials: AR
authors.lastname: de la Serna
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fernandez-Gutierrez
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Ortiz
authors.forename: Gabriel
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.forename: Jose L
authors.initials: JL
authors.lastname: Pablos
authors.forename: Javier
authors.initials: J
authors.lastname: Narvaez
authors.forename: Federico
authors.initials: F
authors.lastname: Navarro
authors.forename: Jose L
authors.initials: JL
authors.lastname: Marenco
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics*; D004268:DNA-Binding Proteins; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D021901:DNA, Intergenic; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3