title: A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Recent genome-wide association studies disclosed that several single nucleotide polymorphisms (SNPs), including tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) (+16860A/G), are associated with the pathophysiology of rheumatoid arthritis (RA). We assessed the usefulness of TRAF1 genotyping as a genetic predictor of the response to anti-TNF treatment in Japanese RA patients.
  
  
  METHODS
  TRAF1 (+16860A/G) was genotyped using the TaqMan SNP genotyping assay in 101 Japanese RA patients treated with anti-TNF drugs for >24 weeks. We retrospectively analysed the association between SNP and the clinical response to treatment. TRAF1 mRNA and protein expression was also evaluated in CD4+, CD8+, CD14+, or CD19+ cells from 25 healthy subjects using quantitative polymerase chain reaction and intracellular staining flow cytometry, respectively.
  
  
  RESULTS
  No statistical difference in DAS28-ESR at baseline was observed between the patient groups with the AA, AG, or GG genotype. The GG genotype was more frequent in non-responders than in good or moderate responders [odds ratio (OR) 7.4, 95% confidence interval (CI) 1.5-37.5]. The non-responders possessed the G allele more frequently than the good or moderate responders (OR 3.5, 95% CI 1.4-9.0). TRAF1 protein expression increased significantly in CD14+ monocytes from healthy subjects with the GG genotype compared with that in subjects with the AA or AG genotype.
  
  
  CONCLUSIONS
  TRAF1 (+16860A/G) may be useful for predicting the clinical response to anti-TNF treatment and may contribute to resistance to treatment in RA patients with the GG genotype by increasing the TRAF1 expression in circulating inflammatory cells.
authors: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. nishi0322@gmail.com.
authors: T
authors: T
authors: Nishimoto
authors: N
authors: N
authors: Seta
authors: R
authors: R
authors: Anan
authors: T
authors: T
authors: Yamamoto
authors: Y
authors: Y
authors: Kaneko
authors: T
authors: T
authors: Takeuchi
authors: M
authors: M
authors: Kuwana
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics; D044466:Asian People / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D047990:TNF Receptor-Associated Factor 1; D014409:Tumor Necrosis Factor-alpha