ASSOCIATION OF THE CD226 (DNAM-1) GLY307SER POLYMORPHISM WITH JUVENILE IDIOPATHIC ARTHRITIS

Background: Recent genetic studies have reported an association of the non-synonymous single nucleotide polymorphism (SNP) Gly307Ser (rs763361) in the CD226 gene with susceptibility to multiple autoimmune diseases, including Type 1 Diabetes, Multiple Sclerosis, Rheumatoid Arthritis, Systemic Lupus Erythematosus and Wegener's Granulomatosis, and a trend towards association with Autoimmune Thyroid Disease. CD226 or DNAM-1 is a type 1 membrane protein belonging to the Ig-superfamily and is involved in the adhesion and co-stimulation of T cells and NK cells. A trend towards association of this SNP with the auto-immune disease Juvenile Idiopathic Arthritis (JIA) was recently reported, but was not statistically significant (p=0.13) (1). Objectives: We performed a case-control genetic association study to investigate whether CD226 Gly307Ser is associated with susceptibility to JIA. Methods: CD226 Gly307Ser was genotyped in 667 JIA cases and 1320 healthy controls, both of North-West-European white origin. Allele frequencies were compared. Patients with oligoarticular (persistent and extended), polyarticular (rheumatoid factor negative and positive) and systemic JIA have been included and were analyzed separately as well as grouped together. A meta-analysis of our study combined with the previously published study was performed. Results: CD226 Gly307Ser was significantly associated with susceptibility to JIA (p(allelic)=0.002, OR=1.23, 95% CI: 1.08-1.41), particularly in the persistent oligoarticular subtype (p(allelic)=0.0008, OR=1.38, 95% CI: 1.14-1.67). Figure 1 shows results per subtype. The meta-analysis (of all subtypes grouped together) confirmed the association with JIA (p(allelic)=0.003, OR=1.13, 95% CI: 1.05-1.22). However, there was some heterogeneity between the two study groups with regard to numbers of included subtypes. Meta-analysis per subtype was not possible due to lacking clinical data. Minor allele frequencies in both Caucasian control groups were comparable (0.47 and 0.46 in our group and in the previously described group respectively). Conclusions: This study provides evidence for a novel JIA susceptibility locus. Additionally, a subtype-specific association of CD226 with persistent oligoarticular JIA has been identified. This finding is in line with the hypothesis that this oligoarticular subtype is not only phenotypically, but also genetically different from the polyarticular subtypes, including extended oligoarthritis. References: 1. Genes Immun. 2010 Mar;11(2):194-8. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 219Session: Genomics, genetics and epigenetics of rheumatic diseases (Poster Presentations )