Background The AGER gene encodes a cell surface multiligand receptor of advanced glycation end‐products that is also capable of binding other molecules and is involved in numerous pathways related to inflammation, apoptosis, immunity and so on. In the present study, we aimed to investigate whether the AGER rs1035798 (G>A) intronic polymorphism, showing an association with multiple sclerosis and rheumatoid arthritis in adults, is related to juvenile idiopathic arthritis (JIA). Methods Caucasian children from the Belarusian population were enrolled in the study. In total, there were 201 cases with JIA, 37 with juvenile systemic lupus erythematosus, 222 children with the articular syndrome of non‐autoimmune etiology (positive control for JIA) and 365 negative controls (children without any autoimmune or inflammatory diseases). Genomic DNA samples from the patients and controls were genotyped by a real‐time polymerase chain reaction. Results A marked association of the homozygous AA rs1035798 genotype with JIA (p = 5 × 10−4) was found. Allele A was also associated with JIA (p = 0.0058), as well as with the articular syndrome of non‐autoimmune etiology (p = 0.0264). The highest frequencies of the AA genotype were found in the subgroups of JIA patients with polyarthritis or severe oligoarthritis. The AA genotype patients also had the smallest mean age of the JIA onset. Conclusions Our results demonstrate that the AGER rs1035798 AA genotype is a risk factor for JIA in Belarusian children. They also suggest a link between the AGER AA genotype and the risk of JIA early onset and severity. However, the functional relevance of the rs1035798 polymorphism is still unclear.

Background Genetic variations of neutrophil cytosolic factor 2 (NCF2), a subunit of NADPH oxidase, are usually associated with chronic granulomatous disease, and their relationship with autoimmune disorders through the defective NADPH oxidase function during phagocytosis is suggested. Our study aimed to explore whether there is an association between the non‐synonymous single nucleotide polymorphism in the NCF2 gene (rs17849502, NC_000001.11:g.183563445G>T) and the development of juvenile autoimmune rheumatic diseases. Methods In order to test this hypothesis, we conducted a pilot case–control study. In total, 709 children and adolescents, all Belarusians, were involved in the study including patients with juvenile‐onset systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), Kawasaki disease (KD), and subjects without autoimmune and inflammatory diseases as the clinical control, as well as health newborns as the population control. Real‐time polymerase chain reaction was used for genotyping. Results The minor T allele of NCF2 occurred most frequently in patients with JSLE (OR = 2.60, 95% CI = 1.18–5.73, p = 0.023 as compared to the clinical control). In groups with JIA and KD, its frequency did not differ from the control. The TT genotype was only observed in 5.7% of patients with JSLE (p = 0.007), but not in other groups. Conclusion Therefore, our study suggested that NCF2 rs17849502 polymorphism is a potential genetic risk factor for JSLE, while it is probably not for such autoimmune rheumatic diseases as JIA or KD.

The IRF5 (interferon regulatory factor 5) gene encoding a transcription factor is involved in the regulation of interferon synthesis and other proinflammatory cytokines. It is assumed that the IRF5 gene is associated with juvenileonset systemic lupus erythematosus (jSLE), a chronic autoimmune disease that develops in childhood and differs from the adult subtype of SLE in a number of its manifestations. The aim of the presented work was to conduct a pilot study of IRF5 rs2004640 polymorphism in the population of children in Belarus and its association with the development of jSLE. Genotyping of DNA samples was performed using real-time PCR in a group of patients diagnosed with jSLE (38 people) and in the clinical control group without autoimmune and inflammatory diseases (378 people). The frequency of the IRF5 rs2004640 minor T allele was determined in the Belarusian population of children (under the age of 17). It was found that the rs2004640 TT genotype is associated with the risk of the jSLE development (OR = 2.27; 95% CI 1.08–4.76; p = 0.035) that after further investigations may improve an early diagnosis of jSLE.

A comparative analysis of three single nucleotide variations of the proteasomal genes PSMA3 (rs2348071) and PSMA6 (rs2277460 and rs1048990) was carried out in the groups of children from 1 to 16 years old with the autoimmune rheumatic disease - juvenile idiopathic arthritis (JIA; n = 199), with articular syndrome of non-autoimmune etiology (n = 229) and in the clinical control group with neither autoimmune nor chronic inflammatory diseases (n = 379). PCR, PCR–RFLP and real-time PCR were used for genotyping. It was found that the CG genotype and G allele of rs10489990 polymorphism (OR = = 1.93; 95 % CI 1.29-2.90; p = 0.002 and OR = 1.51; 95 % CI 1.11-2.04; p = 0.008 respectively), as well as the AA genotype of rs2348071 polymorphism (OR = 1.89; 95 % CI 1.02–3.49; p = 0.044) are associated with the JIA susceptibility, but not with articular syndrome. The established JIA risk genotypes may indicate the involvement of PSMA3 and PSMA6 genes in the development of an autoimmune reaction. In combination with other risk DNA markers, they can be proposed to assess a genetic predisposition to JIA. It was also revealed that the frequencies of risk genotypes and alleles for JIA in the group of patients with articular syndrome as a whole occupy an intermediate position between JIA and control group frequencies. This may indicate an increased JIA risk in some patients with articular syndrome.