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Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis.

Research paper by Anne A Hinks, Paul P Martin, Edward E Flynn, Steve S Eyre, Jon J Packham, Anne A Barton, , Jane J Worthington, Wendy W Thomson

Indexed on: 22 Jul '10Published on: 22 Jul '10Published in: Annals of the rheumatic diseases



Abstract

There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases.To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA.Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane-Armitage trend test implemented in PLINK.One SNP in the LPP gene, rs1464510, showed significant association with JIA (p(trend)=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (p(trend)=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (p(trend)=0.005, OR=1.88, 95% CI 1.2 to 2.94).Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts.