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Multicenter Study
. 2010 Jun;69(6):1049-53.
doi: 10.1136/ard.2009.110650. Epub 2009 Aug 11.

Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis

Anne Hinks  1 , Steve Eyre, Xiayi Ke, Anne Barton, Paul Martin, Edward Flynn, Jon Packham; Childhood Arthritis Prospective Study (CAPS); UKRAG Consortium; BSPAR Study Group; Jane Worthington, Wendy Thomson
Affiliations
Multicenter Study

Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis

Anne Hinks et al. Ann Rheum Dis. 2010 Jun.

Abstract

Background: 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 using 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 with two genes, PTPN22 and IL2RA. Rheumatoid arthritis (RA) is an autoimmune disease that shares similar clinical and pathological features with JIA and, therefore, recently identified confirmed RA susceptibility loci are also excellent JIA candidate loci.

Objective: To determine the overlap of disease susceptibility loci for RA and JIA.

Methods: /st> Fifteen single nucleotide polymorphisms (SNPs) at nine RA-associated loci were genotyped in Caucasian patients with JIA (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: Two JIA susceptibility loci were identified, one of which was a novel JIA association (STAT4) and the second confirmed previously published associations of the TRAF1/C5 locus with JIA. Weak evidence of association of JIA with three additional loci (Chr6q23, KIF5A and PRKCQ) was also obtained, which warrants further investigation.

Conclusion: All these loci are good candidates in view 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.

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Conflict of interest statement

Competing interests: None.

Figures

Figure 1
Figure 1
Plot of allelic odds ratios for minor allele for all previously associated rheumatoid arthritis (RA) single nucleotide polymorphisms (SNPs), comparison with juvenile idiopathic arthritis (JIA). Plots of allelic odds ratios and 95% CI for the association analysis of all SNPs, results in RA (black dots and lines) and in JIA (red dots and lines). STAT4-SNP1, rs11889341; STAT4-SNP2, rs7574865; STAT4-SNP3, rs8179673; STAT4-SNP4, rs10181656. TNFAIP3-SNP1, rs6920220; TNFAIP3-SNP2, rs13207033. TRAF1-SNP1, rs3761847; TRAF1-SNP2, rs10818488; TRAF1-SNP3, rs290018.
See this image and copyright information in PMC

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