Biogenetic Markers for Predicting Response to Immunotherapy in Rheumatoid Arthritis Immunمخلغ



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Submitted Jan 14, 2023
Published Feb 10, 2023
10.24018/ejbiomed.2023.2.1.44

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Background: TNF-α plays a critical role in the pathogenesis of RA. Gene polymorphisms occurring in this pro-inflammatory cytokine or their receptors may influence responses to biological therapy. Objectives: This study aimed to evaluate the impact of -238G/A(rs361525), -308G/A(rs1800629), -376G/A(rs1800750), +489G/A(rs80267059) SNPs in TNF-α and +587T/G(rs1061622), +884A/G(rs5746032) SNPs in TNFRII genes on responsiveness to TNF inhibitors as well as their effect on serum levels of TNF-α and TNFRII. Subjects and methods: Sixty patients with RA treated with anti-TNF therapy (30 responders and 30 non-responders) were allocated to this study. SNPs in the TNF-α and TNFRII genes were studied by three different techniques: PCR-sequencing, PCR-RFLP, and q-PCR-TaqMan assay. TNF-α and TNFRII serum levels were determined using the ELISA technique. Results: TNF-α -308 (GA), +489 (GA), and TNFRII +587 (TG) genotypes were found to be more associated with non-responsiveness to TNF than homozygous genotypes (OR: 1.3, 2.5, and 2.0, respectively). On other hand, TNF-α -238 and -376 (GA) genotypes, were found to be more associated with TNFi responsiveness than homozygous genotypes (OR: 0.172 and 0.22, respectively). However, none of them reached a significant level. Furthermore, the studied SNPs were found to be unrelated to serum levels of TNF-α and TNFRII. Conclusion: According to our findings, the TNF-α -238G/A, -308G/A, -376G/A, +489G/A, and TNFRII +587T/G, +884A/G SNPs were not significantly associated with the responsiveness of RA patients to biological therapy and had no effect on the serum levels of TNF-α and TNFR.

Keywords: rheumatoid arthritis single nucleotide polymorphisms pharmacogenetics TNF-α, TNFRII

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