Polymorphisms in Genes Involved in the Mechanism of Action of Methotrexate: Are They Associated with Outcome in Rheumatoid Arthritis Patients?

Abstract

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. To identify pharmacogenetic markers of outcome in RA patients treated with MTX. We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. 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). MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy.