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AB0015 Genetic Variants Associated with RA Patients and Serotypes in European Populations: Results from Gapaid Project
  1. O. Ruiz-Larrañaga1,
  2. M. Uribarri2,
  3. M.C. Alcaro3,
  4. S. Escorza-Treviño2,
  5. J. del Amo2,
  6. M. Iriondo1,
  7. P. Migliorini4,
  8. L. Czirják5,
  9. A. Estonba1
  1. 1Genetics, Physical Anthropology and Animal Physiology Department, University of the Basque Country, Leioa
  2. 2Department of Research and Development, Progenika Biopharma S.A, Derio, Spain
  3. 3Department of Research and Development, Toscana Biomarkers SrL, Siena
  4. 4Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  5. 5Department of Rheumatology and Immunology, University of Pécs, Medical Center, Pécs, Hungary


Background Rheumatoid arthritis (RA) is one of the most common autoimmune disorders affecting approximately 0.5-1.0% of the population worldwide (1), mainly females. Genetic studies of RA in European ancestry populations, including WGAS and meta-analysis-based works, have identified up to 46 RA risk loci (2-4). Most of them have been identified and validated in RA patients seropositive for ACPA autoantibodies, which are actually considered a well-established diagnostic and prognostic marker for RA. However, little is known about their contribution in seronegative RA disease. In this context, the GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium was created within the European Union's Seventh Framework Programme for Research and Technological Development (FP7), with the aim of validating gene and protein biomarkers for autoimmune diseases such as RA.

Objectives To replicate the association of RA susceptibility loci in an independent European sample and to assess their specificity with ACPA status.

Methods A selection of 64 SNP previously associated with RA have been typed in a cohort of 267 RA patients (169 ACPA-positive and 97 ACPA-negative) and 152 controls from Rheumatology Units of University Hospital of Pisa (Italy) and University of Pécs Medical Center (Hungary). Regression analyses were performed first considering overall RA patients and secondly, taking both serotype subgroups as different disease entities. Results have been adjusted for age, gender and origin of individuals.

Results The well-known CD2, REL, TNFAIP3, IRF5, PTPRC, and CCR6 have been confirmed as RA disease associated loci together with recently discovered BACH2, RASGRP1, and IKZF3 loci, taking all RA patients as a unique phenotype. Results from both serological subgroups separately reflect the specificity of these susceptibility loci and show additional ACPA-positive specific associations for variants at IL6R, IL2RA, BLK, DDX6, IL6, and TLE3 genes.

Conclusions Results from GAPAID project are consistent with previously established RA disease associations for CD2, PTPRC, REL, CCR6, TNFAIP3, IRF5, BLK, IL2RA, and DDX6 loci. In addition, IL6R, BACH2, RASGRP1, TLE3, and IKZF3 are replicated for the first time in an independent European population and IL6 appears to be a suggestive new RA associated locus. The stratified analysis based on ACPA status provides further support for distinct genetic aetiologies of RA subsets, which is clinically relevant since it may have therapeutic implications.


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  2. Stahl et al. Nat Genet. 2010;42(6):508-14.

  3. Zhernakova et al. PLoS Genet 2011;7(2):e1002004.

  4. Eyre et al. Nat Genet 2012;44(12):1336-40.

Disclosure of Interest None declared

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