Background: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. Aim: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. Patients & methods: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. Results: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). Conclusion: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy. © 2014 Future Medicine Ltd.
- 5,10-methylenetetrahydrofolate reductase
- 5-aminoimidazole-4-carboxamide ribonucleotide transformylase
- dihydrofolate reductase
- rheumatoid arthritis
Salazar, J., Moya, P., Altés, A., Díaz-Torné, C., Casademont, J., Cerdà-Gabaroi, D., Corominas, H., & Baiget, M. (2014). Polymorphisms in genes involved in the mechanism of action of methotrexate: Are they associated with outcome in rheumatoid arthritis patients? Pharmacogenomics, 15(8), 1079-1090. https://doi.org/10.2217/pgs.14.67