Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis.
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.
Hinks
Anne
A
Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, Stopford Building, The University of Manchester, Manchester, UK. anne.hinks@manchester.ac.uk
Martin
Paul
P
Flynn
Edward
E
Eyre
Steve
S
Packham
Jon
J
Barton
Anne
A
Worthington
Jane
J
Thomson
Wendy
W
D001171:Arthritis, Juvenile / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide