No evidence for genetic association of interferon regulatory factor 1 in juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) comprises several clinically distinct subgroups and is the most widespread cause of chronic childhood disability. A significant association between JIA and a polymorphism in the interferon regulatory factor 1 (IRF-1) gene has previously been reported, implicating IRF1 in disease susceptibility. The aim of this study was to replicate the IRF1 association in JIA using single-marker and haplotype analyses in a case-control study, using control subjects different from those in the previous study and a larger cohort of patients (n = 765). METHODS: DNA from 765 patients with JIA and 508 unaffected control subjects was genotyped for 4 single-nucleotide polymorphisms in the IRF-1 gene. Association of genotypes at the IRF1 loci was assessed using single-marker and haplotype analyses. RESULTS: No significant differences in genotype frequency or allele frequency were observed between patients and control subjects. CONCLUSION: This replication study used a much larger patient cohort to examine the association of IRF1 in JIA. However, despite the increased statistical power, we observed no significant association for IRF1 markers, either individually or as haplotypes. It is therefore unlikely that this gene is involved in JIA susceptibility.

Novel IL10 gene family associations with systemic juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic childhood disability and encompasses a number of disease subgroups. In this study we have focused on systemic JIA (sJIA), which accounts for approximately 11% of UK JIA cases. This study reports the investigation of three members of the IL10 gene family as candidate susceptibility loci in children with sJIA. DNA from 473 unaffected controls and 172 patients with sJIA was genotyped for a single nucleotide polymorphism (SNP) in IL19 and IL20 and two SNPs in IL10. We examined evidence for association of the four SNPs by single marker and haplotype analysis. Significant differences in allele frequency were observed between cases and controls, for both IL10-1082 (p = 0.031) and IL20-468 (p = 0.028). Furthermore, examination of the haplotypes of IL10-1082 and IL20-468 revealed greater evidence for association (global p = 0.0006). This study demonstrates a significant increased prevalence of the low expressing IL10-1082 genotype in patients with sJIA. In addition, we show a separate association with an IL20 polymorphism, and the IL10-1082A/IL20-468T haplotype. The two marker 'A-T' haplotype confers an odds ratio of 2.24 for sJIA. This positive association suggests an important role for these cytokines in sJIA pathogenesis.