Background: Rheumatoid 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.
Methods: This 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.
Results: The 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).
Conclusions: The 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.
Keywords: Methotrexate; Pharmacogenomics; Rheumatoid arthritis; Treatment efficacy.