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THU0021 Variation at Fcgr2A and Functionally Related Genes is Associated with the Response to Anti-Tnf Therapy in Rheumatoid Arthritis
  1. S. Marsal1,
  2. G. Avila-Pedretti1,
  3. J. Tornero2,
  4. A. Fernández-Nebro3,
  5. F. Blanco4,
  6. I. González-Alvaro5,
  7. J.D. Cañete6,
  8. J. Maymό7,
  9. M. Alperiz8,
  10. B. Fernández-Gutiérrez9,
  11. A. Olivé10,
  12. H. Corominas11,
  13. A. Erra12,
  14. A. Aterido1,
  15. M. Lόpez Lasanta1,
  16. R. Tortosa1,
  17. A. Julià13
  1. 1Hospital Universitari Vall d'Hebron, Barcelona
  2. 2Hospital Universitario Guadalajara, Guadalajara
  3. 3Hospital Regional Universitario Carlos Haya, Málaga
  4. 4Hospital Juan Canalejo, A Coruña
  5. 5Hospital Universitario La Princesa, Madrid
  6. 6Hospital Clínic de Barcelona
  7. 7Hospital del Mar, Barcelona
  8. 8Hospital Universitario Central de Asturias, Asturias
  9. 9Hospital Clínico San Carlos, Madrid
  10. 10Hospital Universitari Germans Trias i Pujol, Badalona
  11. 11Hospital Moisès Broggi, Sant Joan Despí
  12. 12Hospital Sant Rafael
  13. 13Vall Hebron Research Institute, Barcelona, Spain

Abstract

Background Anti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25-30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy.

Objectives We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response.

Methods A total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy.

Results We found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 and RGS12 and the response to adalimumab (rs12356233, P=0.0064 and rs4690093, P=0.040, respectively). In the anti-CCP positive group of patients, we also found a significant association between RGS12 and the response to infliximab (rs2857859, P=0.042).

Conclusions In the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA.

Disclosure of Interest None declared

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