THU0590 The role of stat4 rs7574865 g/t and ifr5 rs2004640 g/t gene polymorphism in juvenile idiopathic arthritis susceptibility among russian paediatricpopulation
Authors: M. Krylov, E. Fedorov, S. Salugina, N. Konovalova, D. Varlamov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the common chronic condition in paediatric population aged under 16 y.o. JIA is an autoimmune disorder with the potential contribution from genetic factors and environmental exposures. Signal transduction and activation of transcription 4 (<i>STAT4</i>) gene and interferon regulatory factor 5 (<i>IRF5</i>) are the common set of susceptibility genes in many autoimmune disorders. <h3>Objectives</h3> To study <i>STAT4</i> rs7574865 G/T and<i> IFR5</i> rs2004640G/T gene polymorphisms impact on JIA susceptibility among Russian children. <h3>Methods</h3> The study included 177 subjects, 66 JIA cases and 111 healthy volunteers (the control group). Mean age of JIA patients was 11.7±4.2 y (3–17 y), mean disease duration was 4.8±3.8 y. All JIA patients were on the record at V. A. Nasonova Research Institute of Rheumatology, meeting ILAR-2001 criteria for JIA diagnosis. JIA group was comprised of 30 (45%) patients with oligoarthritis (oligo-JIA), 20 (30%) patients with polyarthritis (poly-JIA) and 16 (24%) patients with systemic onset arthritis (SoJIA). Oligo-JIA subgroup included 20 (67%) HLA-B27-seropositive patients (JIA-B27), and 10 (34%) patients with anterior uveitis (JIA-uveitis). The variables used for patients classification were: sex (44 girls and 22 boys); disease duration:≤4 years - 34 (51%) patients and &gt;4 years - 32 (49%) patients; the number of joints involved:≤4 - 29 (44.0%) and &gt;4 – 37 (56.0%); positive antibody titers to nuclear antigens (ANA) - 26 (39%) patients. <i>STAT4</i> and <i>IRF5</i> genes polymorphism was studied using real time PCR. <h3>Results</h3> There was no significant difference between JIA and healthy volunteers in the incidence of various genotypes and alleles in the studied range of polymorphisms. The only significant difference was found between the rates of T <i>STAT4</i> allele in oligo-JIA group and T allele in the control group (38% and 20.4%, respectively, <i>p</i>=0.006). Similar differences with the controls in T allele rates were observed in JIA-B27 and JIA-uveitis subgroups (35% and 45% vs 20.4% <i>p</i>=0.044 and <i>p</i>=0.021, respectively). Therefore, carriers of T<i> STAT4</i> allele demonstrate high JIA susceptibility as compared to healthy subjects (OR 2.43 95% CI(1.23–4.70), <i>p</i>=0.007). The risk in JIA-B27 and JIA-uveitis was (OR 2.10 95% CI(0.38–4.60), <i>p</i>=0.070 and OR 3.19 95% CI(1.09–9.06), <i>p</i>=0.021, respectively). There was no specific association between studied gene polymorphisms and increased JIA susceptibility depending on sex, disease duration, number of joints involved and ANA status. <h3>Conclusions</h3> Obtained data confirm the specific role of <i>STAT4</i> rs7574865 G/T polymorphism as the susceptibility factor to oligo-JIA associated with uveitis, HLA-B27 in Russian paediatric population. <h3>Disclosure of Interest</h3> None declared