Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients

PLoS One. 2021 Mar 10;16(3):e0247709. doi: 10.1371/journal.pone.0247709. eCollection 2021.

Abstract

Aim: To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients.

Materials and methods: DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months.

Results: Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs.

Conclusion: No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-analyses are required.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • CpG Islands / genetics
  • DNA Methylation*
  • Epigenome / genetics*
  • Female
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prospective Studies

Substances

  • Antirheumatic Agents
  • Methotrexate

Grants and funding

The author(s) received no specific funding for this work.