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

• Published in: Clinical and experimental rheumatology Vol. 32; no. 2; pp. 211 - 217
• Main Authors: Nishimoto, T, Seta, N, Anan, R, Yamamoto, T, Kaneko, Y, Takeuchi, T, Kuwana, M
• Format: Journal Article
• Language: English
• Published: Italy 01.03.2014
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - pharmacology; Antirheumatic Agents - pharmacology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Asian Continental Ancestry Group - genetics; Female; Genotyping Techniques; Humans; Japan; Male; Middle Aged; Pharmacogenetics - methods; Polymorphism, Single Nucleotide; Predictive Value of Tests; Retrospective Studies; TNF Receptor-Associated Factor 1 - genetics; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Japan
• ISSN: 0392-856X

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. 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. 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. 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.