The potential of TNF and TNFRSF1B gene polymorphism in predicting the clinical response of anti-TNF therapy in patients with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease in children and could lead to severe disability. The aim of this study was to determine the role of gene polymorphisms in predicting the clinical response of anti-TNF therapy in JIA patients. 68 patients with JIA and 20 healthy controls (HC) were included in the study, and patients with JIA received anti-TNF treatment for 24 weeks. Genomic DNA was extracted from peripheral blood of the subjects and five potentially functional SNPs were selected for genotyping (TNF-308 (rs1800629), TNF238 (rs361525), TNFRSF1B (rs1061622), TRAF1/C5 (rs3761847), and PTPN22 (rs2488457)) by PCR methods. No significant genotype frequency differences of TNF-308 (rs1800629), TNF-238 (rs361525), TNFRSF1B (rs1061622), TRAF1/C5 (rs3761847), and PTPN22 (rs2488457) were found between JIA patients and HC. Genotype of TNF-308 GG (rs1800629) and TNFRSF1B TT (rs1061622) were observed to be increased in responders group compared with non-responders group (P=0.034, P=0.048, respectively). Furthermore, univariable logistic regression revealed that TNF-308 A allele (rs1800629) and TNFRSF1B G allele (rs1061622) were risk factors for clinical response (OR: 0.328, 95% CI: 0.117-0.914, P=0.033; OR: 0.387, 95% CI: 0.142-1.055, P=0.063, respectively). However, only TNF-308 A allele (rs1800629) was independent risks for clinical response by multivariable logistic regression (OR: 0.354, 95% CI: 0.142-0.885, P=0.026), while TNFRSF1B G allele (rs1061622) might be potential risks (OR: 0.418, 95% CI: 0.155-1.130, P=0.086). TNF-308 (rs1800629) and TNFRSF1B (rs1061622) variants were potential biomarkers of clinical response in JIA patients treated by anti-TNF drugs.