Polymorfic loci of the non-HLA immune and inflammatory response genes and the risk of the joint pathology development in children in the Republic of Belarus

The variety of causes of the articular syndrome (AS) and the similarity of its clinical manifestation in many diseases significantly complicate the differential diagnosis. Despite the prognosis of the juvenile idiopathic arthritis (JIA) depends on the early diagnosis, there are still no highly specific laboratory tests. Objective: to assess the association of the polymorphic loci of the genes involved into the regulation and implementation of the immune system functions with predisposition to the JIA and other joint pathology in children in the Republic of Belarus. Three groups of children: 275 patients with JIA, 230 patients with joint pathology of various origins, with the exception of JIA and 291 children without autoimmune and chronic inflammatory diseases (control) were genotyped for 11 polymorphic loci of 8 genes: STAT4 (rs7574865), CTLA4 (rs231775), PTPN2 (rs2542151, rs7234029), IL-6 (rs1800795), IL-6R (rs2228145, rs4845618), RUNX1 (rs9979383)) TRAF1/C5 (rs3761847) using real-time PCR and PCR-RFLP. It was found that CC genotype at the rs1800795 locus of the IL-6 gene is associated with the JIA in the general (OR 1.75 [1.18 - 2.58], p = 0.0058), and GG genotype at the rs3761847 locus of the TRAF1/C5 gene - with the systemic JIA (OR 2.79 [1.29 - 6.06], p = 0.01). GG genotype at the rs3761847 locus of the TRAF1/C5 (р = 0.04; OR 1.66 [1.03 - 2.68]) gene and CC genotype (р = 0.0002; OR 2.26 [1.47 - 3.47]) as well as C allele (р = 0.006; OR 2,01 [1.14 - 3.52]) at the rs1800795 locus of the IL-6 gene are associated with early-onset JIA (≤ 5 years). The most common JIA subtypes (oligoarthritis, seronegative polyarthritis, systemic arthritis) differ in the prevalence of allelic variants at the rs3761847 loci of the TRAF1/C5 gene and rs7574865 of the STAT4 gene. JIA patients differ significantly from the AS patients at the following loci: IL-6R (rs2228145, rs4845618), FOXP3 (rs2232365), TRAF1/C5 (rs3761847), as well by the frequencies of 33 paired genotype combinations of the studied polymorphisms. Among JIA patients, sex-dependent features of the genotype distribution in polymorphic variants of the IL-6R (rs2228145, rs4845618) and RUNX1 (rs9979383) genes were revealed. Conclusion. The data obtained indicate genetically determined differences between JIA subtypes as between JIA and AS in case of other joint pathology. This can be used as a basis for the additional criteria development for the differential diagnosis of joint diseases in children.

articular syndrome, juvenile idiopathic arthritis, inflammation, immune response genes, genetic predisposition