Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases

Pharmacogenomics J. 2014 Aug;14(4):356-64. doi: 10.1038/tpj.2014.3. Epub 2014 Apr 8.

Abstract

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Polymorphism, Single Nucleotide

Substances

  • Methotrexate