title: The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population.
abstract: OBJECTIVE
  Genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Caucasian populations have independently identified risk variants in and near the tumor necrosis factor alpha (TNFalpha)-induced protein 3 gene (TNFAIP3), which is crucial for the regulation of TNF-mediated signaling and Toll-like receptor signaling. The aim of this study was to assess the role of TNFAIP3 in the development of SLE and RA in Japanese subjects.
  
  
  METHODS
  We selected 2 single-nucleotide polymorphisms (SNPs) from previous GWA studies. Rs2230926 is a nonsynonymous SNP in TNFAIP3 and is associated with SLE, while rs10499194 is an intergenic SNP associated with RA. We then performed 2 independent sets of SLE case-control comparisons (717 patients and 1,362 control subjects) and 3 sets of RA case-control comparisons (3,446 patients and 2,344 control subjects) using Japanese subjects. We genotyped SNPs using TaqMan assays.
  
  
  RESULTS
  We observed a significant association between rs2230926 and an increased risk of SLE and RA in the Japanese population (for SLE, odds ratio [OR] 1.92, 95% confidence interval [95% CI] 1.53-2.41, P = 1.9 x 10(-8); for RA, OR 1.35, 95% CI 1.18-1.56, P = 2.6 x 10(-5)). The intergenic SNP rs10499194 was also associated with SLE and RA, while the risk allele for RA in Caucasians was protective against the diseases in our population.
  
  
  CONCLUSIONS
  We demonstrated a significant association between the nonsynonymous variant in TNFAIP3 and the risk for SLE and RA in the Japanese population. TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations.
authors.affiliation: Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shimane
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Horita
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Amano
authors.forename: Michito
authors.initials: M
authors.lastname: Hirakata
authors.forename: Akiko
authors.initials: A
authors.lastname: Okamoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Keiko
authors.initials: K
authors.lastname: Myouzen
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000235:genetics*; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D016022:Case-Control Studies; D004268:DNA-Binding Proteins; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3