Associations between gene polymorphisms and treatment outcomes of methotrexate in patients with juvenile idiopathic arthritis

Pharmacogenomics. 2018 Apr;19(6):529-538. doi: 10.2217/pgs-2017-0208. Epub 2018 Mar 28.

Abstract

Aim: Performance of a meta-analysis with respect to the genetic predictors of methotrexate (MTX) treatment outcomes, efficacy and toxicity, in patients with juvenile idiopathic arthritis (JIA).

Methods: Databases of OVID MEDLINE and OVID EMBASE were searched to collect the studies addressing correlations between gene polymorphisms and efficacy and/or toxicity in MTX-treated JIA patients. Pooled odds ratios (ORs) with 95% CIs were estimated in allelic, recessive and/or dominant models.

Results: With regards to efficacy, the C677T (rs1801133) polymorphism in MTHFR was associated with nonresponse to MTX treatment in a recessive model (OR: 0.40; 95% CI: 0.19-0.84). For associations with toxicity, the MTHFR C677T (rs1801133) polymorphism was associated with presenting overall adverse events in an allelic model (OR: 1.54; 95% CI: 1.07-2.22) and a dominant model (OR: 1.70; 95% CI: 1.08-2.68).

Conclusion: C677T (rs1801133) polymorphism in MTHFR predicts nonresponse and/or adverse effects of MTX treatment in JIA patients.

Keywords: adverse event; juvenile idiopathic arthritis; meta-analysis; methotrexate; polymorphism; responsiveness.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / pathology
  • Female
  • Genetic Association Studies
  • Genotype
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Single Nucleotide
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methotrexate