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.
Keywords: 5,10-methylenetetrahydrofolate reductase; 5-aminoimidazole-4-carboxamide ribonucleotide transformylase; ATIC; DHFR; MTHFR; dihydrofolate reductase; methotrexate; rheumatoid arthritis.