Objectives: Genome wide association studies (GWAS) have been extremely successful in the search for susceptibility risk factors for complex genetic autoimmune diseases. As more studies are published, evidence is emerging of considerable overlap of loci between these diseases. In juvenile idiopathic arthritis (JIA), another complex genetic autoimmune disease, the strategy of utilising information from autoimmune disease GWAS or candidate gene studies to help in the search for novel JIA susceptibility loci has been successful, with confirmed association to two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features to JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci.
Methods: Fifteen SNPs at nine RA-associated loci were genotyped in Caucasian JIA patients (n=1054) and controls (n=3531) and tested for association with JIA. Allele and genotype frequencies were compared between cases and controls using the genetic analysis software, PLINK.
Results: We identified two JIA susceptibility loci, one of which is a novel JIA association (STAT4) and the second confirms previously published associations of the TRAF1/C5 locus with JIA. We also present weak evidence of association of JIA to three additional loci (Chr6q23, KIF5A and PRKCQ) that warrant further investigation.
Conclusion: All of these loci represent good candidates in terms of the known pathogenesis of JIA, as genes within these regions (TRAF1, STAT4, TNFAIP3, PRKCQ) are known to be involved in T cell receptor signalling or activation pathways.