Juvenile idiopathic arthritis (JIA) is a multifactorial immune-mediated inflammatory disease in childhood, the most common type of rheumatic disease in children. It is characterized by the polygenic type of hereditary predisposition.Objective: to study the association of STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms with the predisposition to certain JIA subtypes in the Russian pediatric population.Patients and methods. The investigation enrolled 177 patients, including 66 patients diagnosed with JIA and 111 healthy unrelated volunteers (a control group). Of the 66 patients with JIA there were 30 (45%) with oligoarthritis: 20 (67%) with human leukocyte antigen B27(HLA-B27)-positive JIA (that was associated with enthesitis, HLA-B27 positive JIA (JIA-B27), 10 (33%) with anterior uveitis concurrent with antinuclear antibody-positive JIA (JIA-uveitis); 20 (30%) with polyarticular JIA (JIA-poly), seronegative for rheumatoid factor; and 16 (24%) with systemic JIA (JIA-sys). As a control for genotyping STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms, the investigators studied 103 and 111 DNA samples from healthy adult volunteers, respectively. STAT4 rs7574865 G/T and IRF5 rs2004640 G/T polymorphisms were investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results and discussion. In the oligoarticular JIA group, the frequency of the STAT4 T allele was significantly higher than that in the control group (38.3 and 20.4%, respectively; p=0.004). This allele was also significantly more common in the JIA-B27 (35.0 and 20.4%, respectively; p=0.044) and JIA-uveitis (45.0 and 20.4%, respectively; p=0.021) groups compared with the control one. No significant differences were found in the frequency of the mutant STAT4 T allele between the control group and the JIA-sys and JIA-poly groups. Regression analysis showed that the identification of the STAT4 T allele was associated with the high risk of a predisposition to oligoarticular JIA as a whole (odds ratio, OR 2.43; 95% confidence interval (CI) 1.23–4.70; p=0.007), as well as to the antinuclear antibody-positive oligoarticular JIA with uveitis (JIA-uveitis): the risk in T allele carriers was 3.2 times higher than that in the control (OR 3.19; 95% CI 1.09–9.06; p= ). A high risk for predisposition was also found in the JIA-B27 subgroup compared with the control (OR 2.10; 95% CI 0.38–4.60; p=0.070). There were no statistical differences in the frequency of genotypes and alleles of the IRF5 rs2004640 G/T polymorphism between the entire group of JIA as a whole and its individual clinical types, as well as the control group.Conclusion. This pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of oligoarticular JIA, mainly that of JIA-uveitis and JIA-B27.
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