Objective ― The aim of the work was to study the contribution of the immune response mediator genes polymorphism (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, PADI4 rs2240336) to the formation of the predisposition to juvenile idiopathic arthritis (JIA) and its clinical variants. Material and Methods ― The JIA group included 330 patients and the control group – 342 volunteers without autoimmune diseases from the Republic of Bashkortostan, Russia. Genotyping was conducted by the real-time polymerase chain reaction. Results ― Taking into account the differences by sex, it was established, that the alleles/genotypes of the TNFA rs1800629, LTA rs909253, IL2-IL21 rs6822844, PTPN22 rs2476601 polymorphic loci and the TNFA rs1800629*G – LTA rs909253*G haplotype are associated with the development of JIA as a whole (p<0.05); alleles/genotypes of the LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601 polymorphic loci and the TNFA rs1800629*G – LTA rs909253*G haplotype – with some of JIA clinical variants (p<0.05). Conclusion ― In this work, the relationship of the alleles, genotypes and haplotypes of a number of the immune response mediator genes polymorphic loci with the risk of the development of JIA and its clinical variants was established. Specific associations were observed for girls and boys, which indicates the existence of sexual dimorphism in the JIA pathogenesis.

Objective-The aim of the study was to investigate the relationship of the alleles and genotypes of the immune response mediator genes polymorphic loci (rs1800629, rs909253, rs16944, rs6822844, rs2104286, rs1800795, rs1800872, rs3087243, rs755622 rs28362491, rs2240336, rs2476601) with the etanercept efficacy in juvenile idiopathic arthritis (JIA) patients. Material and Methods-The study included 39 JIA patients from Bashkortostan, Russia. Achieving the American College of Rheumatology Pediatric 70 (ACR Pedi 70) response was regarded as the presence of the response to etanercept (otherwise-as the absence), while achieving clinical remission on medication-as the sufficient response (otherwise-as the insufficient). Genotyping was performed using real-time polymerase chain reaction method. Results-The predictors of an increased risk of the non-response to etanercept were the IL1B rs16944*TT (p cor =0.023), NFKB1 rs28362491*II (p cor =0.042) genotypes, and of the increased risk of the insufficient response to etanercept-the IL2RA rs2104286*AA (p cor =0.010), NFKB1 rs28362491*II (p cor =0.026) genotypes. The markers of the decreased risk of the non-response to etanercept were the IL1B rs16944*C (p cor =0.046), NFKB1 rs28362491*D (p cor =0.029) alleles, and of the decreased risk of the insufficient response to etanercept-the IL2RA rs2104286*AG genotype (p cor =0.049), IL2RA rs2104286*G allele (p cor =0.005). Conclusion-In this study the association of the alleles and genotypes of the IL1B rs16944, IL2RA rs2104286, NFKB1 rs28362491 polymorphic loci with the etanercept efficacy in JIA patients was established.

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Background The juvenile (idiopathic) arthritis (JIA) is one of the most common groups of pediatric rheumatic diseases. JIA, as defined by the ILAR, include 7 disease subtypes. Both genetic and environmental factors have been shown to be associated with JIA. Cytokine gene loci are one of the potential susceptibility factors in many immune-inflammatory diseases, such as juvenile arthritis. And patients with JIA had, irrespective of their subclassification, significantly higher levels of pro-inflammatory cytokines. Objectives The goal of the study was to examine evidence for association of the four cytokine genes single nucleotide polymorphisms (SNPs) with different subtypes of JIA. Methods A case-control association study was performed, using tagging SNP approach. DNA of 189 unaffected controls and 103 patients with JIA (32 RF-polyarthritis, 41 persistent oligoarthritis, and 30 other JIA subtypes) from Bashkortostan, Russia, was genotyped for IL1B -511 (rs16944), IL10-592 (rs1800872), TNFA -308 (rs1800629) and LTA +252 (rs909253) SNPs by polymerase chain reaction-restriction fragment length polymorphism method. Results The genotypes distribution was in Hardy-Weinberg equilibrium for all polymorphic genes. The frequencies of LTA and IL10 genotypes investigated did not differ significantly between all affected and control individuals. Variations in genotype frequency were observed between cases and controls for both TNFA and IL1B genes. The TNFA GG and IL1B CC genotypes were prevalence in JIA group (p=0,005, OR=2,534 95%CI 1,299-5,001 and p=0,042, OR=1,781 95%CI 1,025-3,096, correspondingly). And TNFA AG genotype was less frequent in JIA patients (p=0,018, OR=0,449 95%CI 0,227-0,881). Then the JIA individuals were divided in 3 groups: RF-polyarthritis (RFP), persistent oligoarthritis (PO) and others. The distributions of genotypes in RFP and PO groups were similar with overall JIA patients, but the differences with control were not considerable, due to small number of individuals. On the other hand IL1B CC genotype and C allele were associated with high risk of only PO, not with RFP, (pcor=0,028, OR=2,671 95%CI 1,256-5,691 and pcor=0,040, OR=1,989 95%CI 1,149-3,462, correspondingly). Conclusions These findings demonstrate the association of TNFA -308 polymorphism with susceptibility to juvenile (idiopathic) arthritis,and high risk of the persistent oligoarthritis inIL1B -511common SNP variants carriers from Bashkortostan, Russia. These results might have prognostic value for future clinical observations. References Prahalad S., Glass D. A comprehensive review of the genetics of juvenile idiopathic arthritis. Pediatric Rheumatology. 2008; 6 (11). De Jager W. et all. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann. Rheum. Dis. 2007; 66:589–598. Woo P., Colbert R.A. An overview of genetics of paediatric rheumatic diseases. Best Pract. Res. Clin. Rheumatol. 2009; 23(5):589-97. Disclosure of Interest None Declared