title: Association of the X-chromosomal genes TIMP1 and IL9R with rheumatoid arthritis.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is an inflammatory joint disease with features of an autoimmune disease with female predominance. Candidate genes located on the X-chromosome were selected for a family trio-based association study.
  
  
  METHODS
  A total of 1452 individuals belonging to 3 different sample sets were genotyped for 16 single-nucleotide polymorphisms (SNP) in 7 genes. The first 2 sets consisted of 100 family trios, each of French Caucasian origin, and the third of 284 additional family trios of European Caucasian origin. Subgroups were analyzed according to sex of patient and presence of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.
  
  
  RESULTS
  Four SNP were associated with RA in the first sample set and were genotyped in the second set. In combined analysis of sets 1 and 2, evidence remained for association of 3 SNP in the genes UBA1, TIMP1, and IL9R. These were again genotyped in the third sample set. Two SNP were associated with RA in the joint analysis of all samples: rs6520278 (TIMP1) was associated with RA in general (p = 0.035) and rs3093457 (IL9R) with anti-CCP-positive RA patients (p = 0.037) and male RA patients (p = 0.010). A comparison of the results with data from whole-genome association studies further supports an association of RA with TIMPL The sex-specific association of rs3093457 (IL9R) was supported by the observation that men homozygous for rs3093457-CC are at a significantly higher risk to develop RA than women (risk ratio male/female = 2.98; p = 0.048).
  
  
  CONCLUSIONS
  We provide evidence for an association of at least 2 X-chromosomal genes with RA: TIMP1 (rs6520278) and IL9R (rs3093457).
authors.affiliation: Institute of Clinical Immunology and Transfusion Medicine/Center for Biotechnology and Biomedicine (BBZ), Leipzig, Germany. jana.burkhardt@medizin.uni-leipzig.de
authors.forename: Jana
authors.initials: J
authors.lastname: Burkhardt
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
authors.forename: Vitor Hugo
authors.initials: VH
authors.lastname: Teixeira
authors.forename: Holger
authors.initials: H
authors.lastname: Kirsten
authors.forename: Sophie
authors.initials: S
authors.lastname: Garnier
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruehle
authors.forename: Christian
authors.initials: C
authors.lastname: Oeser
authors.forename: Grit
authors.initials: G
authors.lastname: Wolfram
authors.forename: Markus
authors.initials: M
authors.lastname: Scholz
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Renè
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: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Jan
authors.initials: J
authors.lastname: Dequeker
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Radstake
authors.forename: Piet
authors.initials: P
authors.lastname: Van Riel
authors.forename: Leo
authors.initials: L
authors.lastname: van de Putte
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: Bernard
authors.initials: B
authors.lastname: Prum
authors.forename: Ulrike
authors.initials: U
authors.lastname: Buchegger-Podbielski
authors.forename: Frank
authors.initials: F
authors.lastname: Emmrich
authors.forename: Inga
authors.initials: I
authors.lastname: Melchers
authors.forename: François
authors.initials: F
authors.lastname: Cornelis
authors.forename: Peter
authors.initials: P
authors.lastname: Ahnert
mesh_terms: D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D041321:Chromosomes, Human, X / Q000235:genetics*; D005060:Europe; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053651:Receptors, Interleukin-9 / Q000235:genetics*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D044465:White People / Q000208:ethnology / Q000235:genetics
chemical_list: D053651:Receptors, Interleukin-9; D019715:Tissue Inhibitor of Metalloproteinase-1