Polymorphisms in genes involved in the mechanism of action of methotrexate: Are they associated with outcome in rheumatoid arthritis patients?

Juliana Salazar, Patricia Moya, Albert Altés, César Díaz-Torné, Jordi Casademont, Dacia Cerdà-Gabaroi, Hèctor Corominas, Montserrat Baiget

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31 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1079-1090
JournalPharmacogenomics
Volume15
Issue number8
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • 5,10-methylenetetrahydrofolate reductase
  • 5-aminoimidazole-4-carboxamide ribonucleotide transformylase
  • ATIC
  • DHFR
  • dihydrofolate reductase
  • methotrexate
  • MTHFR
  • rheumatoid arthritis

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