Association of PTPRC gene polymorphisms with TNF inhibitor efficacy in rheumatoid arthritis: a systematic review and meta-analysis

Abstract

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint destruction and functional impairment. Tumor Necrosis Factor inhibitors (TNFi) are widely used biologic therapies for RA; however, patient outcomes show significant individual variation. Genetic factors, including polymorphisms in the PTPRC gene, have been investigated as potential predictors of TNFi efficacy, but results remain inconsistent.

Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines to evaluate the association between PTPRC polymorphisms and TNFi treatment response in RA patients. A comprehensive search was performed in PubMed and Scopus databases up to April 2025. Studies were screened and quality assessed using the Q-Genie tool. Meta-analyses employed Mantel-Haenszel methods with fixed and random effects models.

Results: Five studies met eligibility criteria, including data from 12 European cohorts totaling 1,543 RA patients. The main polymorphism assessed was rs10919563. Meta-analysis revealed the rs10919563 A allele was significantly associated with increased odds of non-response to TNFi (allelic model OR: 1.94; 95%CI: 1.31-2.88). The recessive models supported these findings, and no publication bias was detected.

Conclusions: Our results consolidate evidence supporting the PTPRC rs10919563 polymorphism as a potential predictive genetic biomarker for TNFi efficacy in RA, which could be integrated into personalized treatment strategies. Further studies are required to validate clinical utility across diverse populations.

Keywords

Rheumatoid arthritis / PTPRC gene / tumor necrosis factor inhibitors (TNFi) / genetic polymorphisms / treatment response biomarkers

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