Variations in Genetic Factors Impacting the Effectiveness and Side Effects of Methotrexate with Rheumatoid Arthritis

This review provides a comprehensive overview of genetic variations influencing the effectiveness and side effects of methotrexate (MTX) treatment in rheumatoid arthritis (RA) patients. It synthesizes findings on associations between genetic polymorphisms and MTX therapy outcomes, aiming to identify potential genetic markers for enhancing treatment and personalized strategies in RA. The review highlights genetic variations associated with MTX therapy effects. Variants in genes involved in MTX transport, including reduced folate carrier 1 (RFC1) and ABC transporters, correlate with treatment response. Specific RFC1 and ABCB1 variants are linked to improved MTX efficacy. Polymorphisms in genes regulating MTX metabolism, such as thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR), predict effectiveness and toxicity risks of MTX. Additionally, genes influencing MTX's mechanistic pathways, like the adenosine signaling cascade, impact clinical outcomes. While the evidence is preliminary, this review suggests the potential of genetic testing to guide personalized MTX therapy in RA, leading to improved effectiveness and reduced adverse events. However, further research with diverse cohorts is necessary to validate these findings and establish the utility of pharmacogenomic-based treatment approaches for RA patients receiving MTX. RA is a chronic autoimmune disease treated with MTX as the cornerstone therapy, but patient responses vary. This comprehensive review examines genetic variations influencing MTX's efficacy and toxicity in RA patients. Through a rigorous literature review using databases like PubMed and Web of Science, this study synthesizes findings from pharmacogenetic research on genetic polymorphisms and MTX outcomes.