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AB0093 Association of cd247 polymorphisms with rheumatoid arthritis: a replication study and a meta-analysis
  1. M. Teruel1,
  2. C. McKinney2,
  3. A. Balsa3,
  4. D. Pascual-Salcedo4,
  5. L. Rodriguez-Rodriguez5,
  6. A. M. Ortiz6,
  7. C. Gómez-Vaquero7,
  8. M. A. González-Gay8,
  9. M. Smith9,
  10. T. Witte10,
  11. T. R. Merriman11,
  12. B. A. Lie12,
  13. J. Martin1
  1. 1Instituto de Parasitología Y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain
  2. 2Department of Biochemistry, University of Otago, Dunedin, New Zealand
  3. 3Rheumatology Service
  4. 4Immunology Service, Hospital Universitario La Paz
  5. 5Rheumatology Service, Hospital Clínico San Carlos
  6. 6Rheumatology Service, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Madrid
  7. 7Rheumatology Service, Hospital Universitari Bellvitge, Barcelona
  8. 8Rheumatology Division, Hospital UniversitarioMarqués de Valdecilla, IFIMAV, Santander, Spain
  9. 9Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide, Australia
  10. 10Clinic for Immunology and Rheumatology, Medical School Hannover, Hannover, Germany
  11. 11Department of Biochemistry, University of Otago, Dunedin, New Zealand
  12. 12Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway


Background The T-cell receptor T3 zeta chain (CD3ζ), also called CD247, is essential for assembly, surface expression and signaling cascade of the T-cell receptor-CD3 complex (TCR/CD3 complex). Abnormalities in this pathway can result in T-cell dysfunction and development of autoimmune disorders [1]. Regarding this, previous reports have demonstrated an association of CD247 variants with systemic lupus erythematosus [2, 3] and systemic sclerosis [4, 5]. In the case of rheumatoid arthritis (RA), one meta-GWAS found no association between CD247 gene and RA at a genome-wide level of significance [6], however, a more recent meta-analysis of GWAS on RA and celiac disease (CeD) identified CD247 gene as a new susceptibility locus for RA [7].

Objectives In order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large independent European Caucasian population.

Results However, no evidence of association was found for these three CD247 SNPs with RA and with the anti-cyclic citrullinated polypeptide (anti-CCP) status. We performed a meta-analysis including GWAS data for the rs864537 from previously published data, reveling an overall genome-wide significant association between rs864537 and RA with anti-CCP (OR 0.90 [0.87 to 0.93], Poverall= 2.1 x 10-10).

Conclusions Our results described for first time at GWAS-level the association of this CD247 variant and RA risk

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  7. Zhernakova A et al. PLoS Genet. 2011; 7:e1002004.

Acknowledgements This work was supported by two Spanish grants from RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), within the VI PN de I+D+i 2008-2011 (FEDER) and also by grants from the European IMI BTCure Program. MT was supported by Spanish Ministry of Science through the program Juan de la Cierva (JCI-2010-08227).

Disclosure of Interest None Declared

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