IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA)

CER3953
2010 Vol.28, N°6
PI 0912, PF 0918
Paediatric Rheumatology

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PMID: 21205466 [PubMed]

Received: 27/06/2010
Accepted : 23/09/2010
In Press: 04/01/2011
Published: 04/01/2011

Abstract

OBJECTIVES:
Juvenile idiopathic arthritis (JIA) is a rare, but severe cause of childhood disability. Systemic onset JIA (SoJIA) accounts for approximately 5.8% of all JIA cases and is associated with cytokine dysregulation, including interleukin (IL-)1, IL-6 and tumour necrosis factor (TNF-)α. IL-10 is an immuno-regulatory cytokine, which in part regulates inflammation by controlling inflammatory cytokine expression. Dysregulation in IL-10 expression and certain single nucleotide polymorphisms (SNPs) in the IL-10 promoter were shown to be associated with autoimmune and infectious diseases.
METHODS:
Genomic DNA-samples from SoJIA patients from two German Paediatric Rheumatology centres, and healthy controls were analysed for three well defined IL-10 promoter SNPs (-1082G>A, -819C>T, and -592C>A). These SNPs are in tight linkage disequilibrium, and result in three predominant (or `classical`) haplotypes: ATA, ACC, and GCC. ATA and ACC are associated with low and medium, GCC is associated with high IL-10 expression.
RESULTS:
Here, we show a strong association of IL-10 promoter polymorphisms with SoJIA. We demonstrate a significantly increased frequency of low IL-10 expressing -1082A/A alleles, the medium IL-10 expressing ACC haplotype (p=0.01), and an enrichment of the rare GTC haplotype (p<0.001) in patients with SoJIA. Heterozygous -1082G/A alleles (p<0.001), and the GCC haplotype (p<0.001) on one allele protect from developing SoJIA.
CONCLUSIONS:
This suggests a central role of the immuno-regulatory cytokine IL-10 in the pathogenesis of SoJIA.