A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis

Tetsuya Nishimoto, Noriyuki Seta, Ryusuke Anan, Tatsuya Yamamoto, Yuko Kaneko, Tsutomu Takeuchi, Masataka Kuwana

Research output: Contribution to journalArticle

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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. Conclusion: 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.

Original languageEnglish
Pages (from-to)211-217
Number of pages7
JournalClinical and Experimental Rheumatology
Volume32
Issue number2
Publication statusPublished - 2014

Fingerprint

TNF Receptor-Associated Factor 1
Single Nucleotide Polymorphism
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Genotype
Healthy Volunteers
Therapeutics
Odds Ratio
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Confidence Intervals
Genome-Wide Association Study
Monocytes
Flow Cytometry
Proteins
Alleles
Staining and Labeling
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

A single nucleotide polymorphism of TRAF1 predicts the clinical response to anti-TNF treatment in Japanese patients with rheumatoid arthritis. / Nishimoto, Tetsuya; Seta, Noriyuki; Anan, Ryusuke; Yamamoto, Tatsuya; Kaneko, Yuko; Takeuchi, Tsutomu; Kuwana, Masataka.

In: Clinical and Experimental Rheumatology, Vol. 32, No. 2, 2014, p. 211-217.

Research output: Contribution to journalArticle

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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. Conclusion: 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.",
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