The Influence of TNFRSF1B, PADI4, and miRNA 499 Gene Polymorphisms on Susceptibility and Responsiveness to TNF Inhibitors in Patients with Rheumatoid Arthritis

Background Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes joint deterioration. Over the past decade, the primary approach to treat RA has relied on biological medications. Despite confirming the effectiveness of this therapy, patients have shown significant diversity in their clinical responses to treatment. This variability can be attributed to various genetic polymorphisms that influence the response to biological drugs. This study was conducted to investigate whether TNFRSF1B (rs1061622), PADI4 (rs1748033), and miRNA 499 (rs3746444) gene polymorphisms are associated with susceptibility and responsiveness to TNF-α inhibitors in RA patients. Materials Methods: 100 RA patients (50 responders and 50 non-responders) and 100 apparently healthy subjects as the control group were studied. Genotyping of the polymorphisms was carried out using real-time polymerase chain reaction (PCR) with the TaqMan allelic discrimination assay. Results: The frequency of TG (P0.039) and GG genotypes of TNFRSF1B (rs1061622) were higher in RA patients than in the control group. At the alleles level the mutant G allele was significantly more frequent among patients than control group (P=0.018). For PADI4 (rs1748033), the mutant C allele was more frequent among patients than controls (P=0.041). Sub-dividing of patients into responders and non-responders revealed that the mutant homozygous CC genotype of PADI4 (rs1748033) was significantly more frequent in non-responders than responders patients (P=0.046). AG genotype (P=0.016) and G allele (P=0.036) of miRNA 499a (rs3746444) were more frequent in non-responders than responders. Conclusion: Variant genotypes of TNFRII (Rs1061622) and PADI4 (rs1748033), may be associated with an increased risk of RA while PADI4 (rs1748033) and miRNA-499a (rs3746444) polymorphism may be associated with non-response to infliximab.