A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register

Pharmacogenomics J. 2012 Apr;12(2):128-33. doi: 10.1038/tpj.2010.80. Epub 2010 Oct 5.


Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cohort Studies
  • DNA-Binding Proteins / genetics*
  • Genetic Markers*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Registries
  • Tumor Necrosis Factor alpha-Induced Protein 3


  • Antirheumatic Agents
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • oligodendrocyte lineage transcription factor 3, human
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Methotrexate