Original Article | Published:

A genome-wide association study identifies a new locus associated with the response to anti-TNF therapy in rheumatoid arthritis

The Pharmacogenomics Journal volume 16, pages 147150 (2016) | Download Citation

Abstract

Anti-Tumor Necrosis Factor (anti-TNF) drugs are biologic agents commonly used to treat rheumatoid arthritis (RA). However, anti-TNFs are not effective in approximately one out of four treated patients. We conducted a Genome-Wide Association Study (GWAS) to identify the genetic variation associated with the response to anti-TNF therapy in RA. In the discovery stage, 372 RA patients treated with an anti-TNF agent (infliximab, adalimumab or etanercept) were analyzed and treatment response was defined at 12 weeks of therapy. We found a genome-wide significant association in the MED15 gene with the response to etanercept (P<1.5e-8). Using an independent cohort of 245 RA patients, we performed a replication study of the most significant GWAS associations. We replicated the association at the MED15 locus and found suggestive evidence of association in the previously associated MAFB locus. The results of this study suggest novel mechanisms associated with the response to anti-TNF therapies.

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Acknowledgements

This work was supported by the Spanish Ministry of Economy and Competitiveness Strategic Project grants (PSE-010000-2006-6 and IPT-010000-2010-36). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Affiliations

  1. Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, Barcelona, Spain

    • A Julià
    • , I Acosta-Colman
    • , A Alonso
    • , M López-Lasanta
    • , R Tortosa
    •  & S Marsal
  2. UGC Reumatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain

    • A Fernandez-Nebro
  3. Rheumatology Service, INIBIC-Hospital Universitario A Coruña, A Coruña, Spain

    • F Blanco
  4. Rheumatology Service, Hospital Universitario La Princesa, IIS Princesa, IIS La Princesa, Madrid, Spain

    • A Ortiz
  5. Rheumatology Service, Hospital Clínic de Barcelona, Barcelona, Spain

    • J D Cañete
  6. Rheumatology Service, Hospital del Mar, Barcelona, Spain

    • J Maymó
  7. Rheumatology Service, Hospital Universitario Central de Asturias, Oviedo, Spain

    • M Alperi-López
  8. Rheumatology Service, Hospital Clínico San Carlos, Madrid, Spain

    • B Fernández-Gutierrez
  9. Rheumatology Service, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain

    • A Olivè
  10. Rheumatology Service, Hospital Moisès Broggi, Barcelona, Spain

    • H Corominas
  11. Rheumatology Service, Hospital Sant Rafael, Barcelona, Spain

    • A Erra
  12. Rheumatology Service, Hospital Universitario De Guadalajara, Guadalajara, Spain

    • J Tornero

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The authors declare no conflict of interest.

Corresponding author

Correspondence to S Marsal.

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DOI

https://doi.org/10.1038/tpj.2015.31

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj)

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