FCGR polymorphisms in the treatment of rheumatoid arthritis with Fc-containing TNF inhibitors

Pharmacogenomics. 2015;16(4):333-45. doi: 10.2217/pgs.14.175.


Objectives: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other FcγR functional polymorphisms.

Methods: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting.

Results: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5).

Conclusion: None of the three functional polymorphisms in FcγR genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies. Original submitted 17 September 2014; Revision submitted 9 December 2014.

Keywords: FCGRT; Fc receptor; TNF inhibitors; adalimumab; biologics; biomarkers; etanercept; genetics; infliximab; rheumatoid arthritis.

Publication types

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

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Receptors, Fc / genetics*
  • Receptors, IgG / genetics*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • FCGR2B protein, human
  • FCGR3A protein, human
  • Histocompatibility Antigens Class I
  • Receptors, Fc
  • Receptors, IgG
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Fc receptor, neonatal