ArticleArthritis research & therapy2026
The association between methotrexate metabolism-related gene polymorphisms and therapeutic efficacy and toxicity in patients with rheumatoid arthritis.
Article in Arthritis research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetrical joint inflammation and destruction. Methotrexate (MTX) is a first-line treatment, but about 40% of patients need to switch to other disease-modifying antirheumatic drugs (DMARDs) due to inadequate efficacy or adverse effects. Pharmacogenomic studies have shown that genotypes may affect drug metabolism, efficacy, and toxicity.
methodsThis study analyzed the correlation between MTX metabolism-related genes, including SLC19A1, ABCB1, SLCO1B1, and MTHFR, and efficacy in 84 RA patients treated with MTX, using the chi-square test or Fisher’s exact test combined with three gene models.
resultsThe results showed that the 129 bp insertion allele of the SLC19A1 gene was associated with drug efficacy. Compared with the X/X genotype, patients carrying at least one INS-allele (INS/INS + X/ins) would have higher odds of showing improvement (p = 0.047, OR = 2.564, 95% CI = 0.999–6.580). The CTTGTACTTGTA of rs4149096 and the C-allele of rs2291075 were associated with improvement (p = 0.036, OR = 4.145, 95% CI = 1.028–16.715), but the same allele was negatively associated with good response (p = 0.036, OR = 0.188, 95% CI = 0.042–0.827).
conclusionsThe rs4149096 and rs2291075 showed significant differences between moderate response and no response, as well as between good and moderate responders; however, no significant association was observed between improvement and no response, reflecting a typical nonlinear dose-response effect. The 129 bp insertion of the SLC19A1 gene was positively correlated with better treatment response, suggesting it may be more directly involved in MTX carriage or metabolism, exerting a stable additive effect on drug efficacy. In conclusion, these results highlight the importance of MTX-related genotypes in treatment improvement and intensity, and support their potential as predictive markers of treatment response.
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