Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis

Pharmacogenomics J. 2016 Apr;16(2):137-40. doi: 10.1038/tpj.2015.29. Epub 2015 Apr 21.


Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Female
  • Genetic Association Studies
  • Genetic Markers
  • Humans
  • I-kappa B Kinase / genetics*
  • Infliximab / therapeutic use
  • Interleukin-10 / genetics*
  • Leukocyte Common Antigens / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Genetic Markers
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Infliximab
  • CHUK protein, human
  • I-kappa B Kinase
  • Leukocyte Common Antigens
  • PTPRC protein, human
  • Adalimumab