ASSOCIATION OF CD247 POLYMORPHISMS WITH RHEUMATOID ARTHRITIS: A REPLICATION STUDY AND A META-ANALYSIS

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). Conclusions: Our results described for first time at GWAS-level the association of this CD247 variant and RA risk References: 1.Takeuchi T et al. Ann Rheum Dis. 2012; 71:i78-i81. 2.Gorman CL et al. J Immunol. 2008; 180: 1060-70. 3.Warchol T et al. Tissue Antigens. 2009; 74:68-72. 4.Dieude P et al. Ann Rheum Dis. 2011;70:1695-6. 5.Radstake TR et al. Nat Genet. 2010; 42:426-9. 6.Stahl EA et al. Nat Genet. 2010; 42:508-14. 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 DeclaredCitation: , volume 72, supplement s3, year 2013, page Session: Publication only ( )