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

Journal article

BACKGROUND: There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. OBJECTIVE: To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Authors: Hinks, A; Martin, P; Flynn, E; Eyre, S; Packham, J

• Journal: Annals of the rheumatic diseases
• Volume: 69
• Issue: 12
• Pages: 2169-2172
• Publication date: 2010-12-01
• DOI: 10.1136/ard.2009.126938
• EISSN: 1468-2060
• ISSN: 0003-4967
• Language: English
• Keywords: Gene Frequency; Diabetes Mellitus, Type 1; Celiac Disease; Genetic Predisposition to Disease; Case-Control Studies; Polymorphism, Single Nucleotide; Female; Male; Arthritis, Juvenile Rheumatoid; Humans; Genotype; Autoimmune Diseases; Childhood Arthritis Prospective Study (CAPS), UKRAG Consortium, BSPAR study group