title: IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA).
abstract: OBJECTIVE
  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.
authors.affiliation: Pediatric Rheumatology and Immunology Section, University Children's Hospital Dresden, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
authors.forename: J C
authors.initials: JC
authors.lastname: Möller
authors.forename: D
authors.initials: D
authors.lastname: Paul
authors.forename: G
authors.initials: G
authors.lastname: Ganser
authors.forename: U
authors.initials: U
authors.lastname: Range
authors.forename: M
authors.initials: M
authors.lastname: Gahr
authors.forename: R
authors.initials: R
authors.lastname: Kelsch
authors.forename: A
authors.initials: A
authors.lastname: Rösen-Wolff
authors.forename: C M
authors.initials: CM
authors.lastname: Hedrich
mesh_terms: D000293:Adolescent; D000483:Alleles; D001171:Arthritis, Juvenile / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D016753:Interleukin-10