title: Association of TNFAIP3 interacting protein 1, TNIP1 with systemic lupus erythematosus in a Japanese population: a case-control association study.
abstract: BACKGROUND
  TNFAIP3 interacting protein 1, TNIP1 (ABIN-1) is involved in inhibition of nuclear factor-κB (NF-κB) activation by interacting with TNF alpha-induced protein 3, A20 (TNFAIP3), an established susceptibility gene to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Recent genome-wide association studies revealed association of TNIP1 with SLE in the Caucasian and Chinese populations. In this study, we investigated whether the association of TNIP1 with SLE was replicated in a Japanese population. In addition, association of TNIP1 with RA was also examined.
  
  
  METHODS
  A case-control association study was conducted on the TNIP1 single nucleotide polymorphism (SNP) rs7708392 in 364 Japanese SLE patients, 553 RA patients and 513 healthy controls.
  
  
  RESULTS
  Association of TNIP1 rs7708392C was replicated in Japanese SLE (allele frequency in SLE: 76.5%, control: 69.9%, P = 0.0022, odds ratio [OR] 1.40, 95% confidence interval [CI] 1.13-1.74). Notably, the risk allele frequency in the healthy controls was considerably greater in Japanese (69.9%) than in Caucasians (24.3%). A tendency of stronger association was observed in the SLE patients with renal disorder (P = 0.00065, OR 1.60 [95%CI 1.22-2.10]) than in all SLE patients (P = 0.0022, OR 1.40 [95%CI 1.13-1.74]). Significant association with RA was not observed, regardless of the carriage of human leukocyte antigen DR β1 (HLA-DRB1) shared epitope. Significant gene-gene interaction between TNIP1 and TNFAIP3 was detected neither in SLE nor RA.
  
  
  CONCLUSIONS
  Association of TNIP1 with SLE was confirmed in a Japanese population. TNIP1 is a shared SLE susceptibility gene in the Caucasian and Asian populations, but the genetic contribution appeared to be greater in the Japanese and Chinese populations because of the higher risk allele frequency. Taken together with the association of TNFAIP3, these observations underscore the crucial role of NF-κB regulation in the pathogenesis of SLE.
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. a-kawasaki@umin.net
authors.forename: Aya
authors.initials: A
authors.lastname: Kawasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Makio
authors.initials: M
authors.lastname: Kusaoi
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Robert R
authors.initials: RR
authors.lastname: Graham
authors.forename: Kunio
authors.initials: K
authors.lastname: Matsuta
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Behrens
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C117046:TNIP1 protein, human; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3