Background Juvenile idiopathic arthritis (JIA) is a generic term for arthritis that has an onset before the age of 16 and persists for more than 6 weeks. JIA is probably a collection of diseases with complex overlapping etiologies, with each subtype influenced by multiple genetic susceptibility loci and mediated by environmental effects [1]. Such genes as IL10, IL2RA [2], IL2-21 [3], show some evidence of association with clinically distinct autoimmune phenotypes in different populations.

Objectives The goal of the study was to test the hypothesis that variants of IL10, IL2RA, IL2-21 genes could underlie susceptibility to different subtypes of JIA in patients from Russia.

Methods Allele and genotype frequencies of IL10 (rs1800872), IL2RA (rs2104286), IL2-21 (rs6822844) SNPs were assessed using RCR-RFLP method. A cohort of 135 JRA patients and 97 healthy controls from Bashkortostan, Russia was tested. Patients were diagnosed according to the ILAR criteria [4]. There were 58 persistent oligoarthritis, 40 rheumatoid factor (RF)-negative polyarthritis and 38 other subtypes patients. Chi-square (χ²) test and odds ratio (OR) were estimated to evaluate the association.

Results All SNPs were in Hardy Weinberg Equilibrium. The genotype CC and allele C of IL10 conferred risk to the JIA cohort as a whole (p=0,007, OR=2,203 95%CI 1,287-3,769 and p=0,006, OR=1,824 95%CI 1,210-2,749, correspondingly). A dominant model improved the OR (for AA+CA genotypes p=0,0041, OR=0,46 95%CI 0,27-0,79). When analyses were repeated after stratification by subtypes, the data were significant only in the persistent oligoarthritis cohort: the genotype CC and allele C at IL10 SNP were associated with disease susceptibility (p=0,003, OR=3,057 95%CI 1,527-6,122 and p=0,003, OR=2,541 95%CI 1,442-4,476, correspondingly). But this patients group was the biggest. For the IL2RA and IL2-21 polymorphisms no difference was observed in allele and genotype frequencies between JIA patients and controls.

Conclusions We have demonstrated associations of IL10 variant with persistent oligoarthritis in patients from Bashkortostan, Russia. Our results confirmed partly that clinically distinct autoimmune phenotypes share common genetic susceptibility factors in JIA patients.

1. Glass DN, Giannini EH. Juvenile rheumatoid arthritis as a complex genetic trait. Arthritis Rheum. 1999. Nov;42(11):2261-8.

2. Hinks A, Ke X, Barton A, Eyre S, Bowes J, Worthington J, Thompson SD, Langefeld CD, Glass DN, Thomson W; UK Rheumatoid Arthritis Genetics Consortium;British Society of Paediatric and Adolescent Rheumatology Study Group. Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis Rheum. 2009. Jan;60(1):251-7.

3. Hinks A, Eyre S, Ke X, Barton A, Martin P, Flynn E, Packham J, Worthington J. Childhood Arthritis Prospective Study; UKRAG Consortium; BSPAR Study Group, Thomson W. Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis. Genes Immun. 2010. Mar;11(2):194-8.

4. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P. International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004. Feb;31(2):390-2.

Disclosure of Interest None Declared