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

Abstract

OBJECTIVES:

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: T Nishimoto, N Seta, R Anan, T Yamamoto, Y Kaneko, T Takeuchi, M Kuwana
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2014 Mar-Apr Vol. 32 Issue 2 Pg. 211-7 ISSN: 0392-856X [Print] Italy
• PMID: 24321457 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• TNF Receptor-Associated Factor 1
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (pharmacology)
• Antirheumatic Agents (pharmacology)
• Arthritis, Rheumatoid (drug therapy, genetics)
• Asian People (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)