Article Text

other Versions

PDF
Overlap of disease susceptibility loci for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA).
  1. Anne Hinks (anne.hinks{at}manchester.ac.uk)
  1. University of Manchester, United Kingdom
    1. Steve Eyre (steve.eyre{at}manchester.ac.uk)
    1. University of Manchester, United Kingdom
      1. Xiayi Ke (xiayi.ke{at}manchester.ac.uk)
      1. University of Manchester, United Kingdom
        1. Anne Barton (anne.barton{at}manchester.ac.uk)
        1. University of Manchester, United Kingdom
          1. Paul Martin (paul.martin-2{at}manchester.ac.uk)
          1. University of Manchester, United Kingdom
            1. Edward Flynn (edward.flynn{at}manchester.ac.uk)
            1. University of Manchester, United Kingdom
              1. Jon Packham (jon.packham{at}uhns.nhs.uk)
              1. Haywood Hospital, United Kingdom
                1. Jane Worthington (jane.worthington{at}manchester.ac.uk)
                1. University of Manchester, United Kingdom
                  1. Wendy Thomson (wendy.thomson{at}manchester.ac.uk)
                  1. University of Manchester, United Kingdom

                    Abstract

                    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.

                    Statistics from Altmetric.com

                    Request permissions

                    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.