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

被引:1
作者
Moeller, J. C.
Paul, D.
Ganser, G. [2 ]
Range, U. [3 ]
Gahr, M.
Kelsch, R. [4 ]
Roesen-Wolff, A.
Hedrich, C. M. [1 ]
机构
[1] Tech Univ Dresden, Univ Childrens Hosp Dresden, Dept Paediat Rheumatol & Immunol, Paediat Rheumatol & Immunol Sect, D-01307 Dresden, Germany
[2] St Josef Stift Sendenhorst, NW German Ctr Rheumatol, Dept Paediat & Adolescent Rheumatol, Sendenhorst, Germany
[3] Tech Univ Dresden, Inst Med Informat & Biometr, Dresden, Germany
[4] Univ Hosp Munster, Inst Transfus Med & Transplant Immunol, Munster, Germany
关键词
IL-10; systemic onset JIA; Still's disease; inflammation; polymorphism; SNP; cytokine; INTERLEUKIN-10; PRODUCTION; IL-10; EXPRESSION; GENE; PREDISPOSITION; SUSCEPTIBILITY; TRANSCRIPTION; HAPLOTYPES; CYTOKINES; FAMILY;
D O I
暂无
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-)alpha. 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 polymorphistns (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. Conclusion This suggests a central role of the immuno-regulatory cytokine IL-10 in the pathogenesis of SoJIA.
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页码:912 / 918
页数:7
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