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Genetic determinants for methotrexate response in juvenile idiopathic arthritis

Serena Pastore1, Gabriele Stocco2, Diego Favretto1

  • 1Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.

Frontiers in Pharmacology
|April 9, 2015
PubMed

Insights

Juvenile idiopathic arthritis (JIA) treatment with methotrexate is often ineffective, as many children do not respond. Identifying genetic markers could personalize methotrexate therapy for JIA patients, improving treatment outcomes.

Area of Science:

  • Rheumatology
  • Pharmacogenetics
  • Pediatric Medicine

Background:

  • Juvenile idiopathic arthritis (JIA) is a leading cause of chronic childhood rheumatic disease and disability.
  • Methotrexate, a folic acid analog, is the primary disease-modifying anti-rheumatic drug for JIA.
  • A significant proportion of JIA patients (35-45%) exhibit inadequate response to methotrexate therapy.

Purpose of the Study:

  • To explore molecular elements, specifically genetic variants, that influence methotrexate response in JIA.
  • To identify potential genetic markers for individualizing methotrexate treatment strategies in children with JIA.
  • To review existing studies on candidate gene variants and recent genome-wide approaches for methotrexate response in JIA.

Main Methods:

  • Review of studies evaluating candidate genetic variants in methotrexate pharmacodynamics and pharmacokinetics in JIA.
  • Analysis of recent genome-wide association studies (GWAS) to identify novel biological pathways.
  • Exploration of potential integration of genomic data with deep sequencing, epigenetics, and pharmacokinetics.

Main Results:

  • Previous studies on candidate genetic variants yielded contrasting and inconclusive results.
  • No definitive genetic marker for methotrexate response in JIA has been established for clinical use.
  • Genome-wide approaches suggest involvement of pathways like TGF-beta signaling and calcium channels in methotrexate response.

Conclusions:

  • Personalizing methotrexate therapy for JIA requires identifying reliable genetic markers.
  • Further validation of genomic findings and integration with advanced analyses are crucial.
  • Future research integrating deep sequencing, epigenetics, and pharmacokinetics holds promise for tailoring methotrexate treatment in JIA.

Keywords:
gene expression profilinggenome-wide association studyjuvenile idiopathic arthritismethotrexatepharmacogenomics

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