BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by autoimmune inflammatory response focused in the synovium. RA is a complex disorder with significant genetic component and it is also known to have possible environmental triggers. Microbiota and bacterial infections play a significant role in RA etiology. The onset of RA may be accompanied by the previous or ongoing chlamydia infection in some cases.Objectivesto determine genetic variants of susceptibility to RA in Belarusian populationMethods650 individuals were divided into 2 cohorts: 305 patients with RA (59.69 ± 12.20), and 345 controls (mean age 37.42 ± 10.62). Patients with RA were further stratified into two subsets – those with catamnestic Chlamydia trachomatis/Chlamydophila pneumoniae infection (43, “RAChl+”) and those without (262, “RAChl-“). 11 SNPs of 10 genes (IL6 (rs1800795), IL6R (rs2228145 and rs4845618), STAT4 (rs7574865), TRAF1/C5 (rs3761847), RUNX1 (rs9979383), RUNX3 (rs11249215), PTPN2 (rs2542151), PTPN22 (rs2476601), AGER (rs1035798), SLC7A11 (rs13128867)) were genotyped using Real-time PCR or PCR-RFLP.ResultsIt was found that homozygous TT genotype at the rs7574865 locus of the STAT4 gene and CT+TT genotypes at the rs2476601 locus of the PTPN22 gene are associated with RA in general (OR 2.71 [1.31 – 5.61]; p = 0.005 and OR 2.47 [1.75-3.48] p<0.000, respectively). CC genotype at the rs9979383 locus of the RUNX1 gene and AG+GG genotypes at the rs11249215 locus of the RUNX3 gene revealed protective effect (OR 0.63 [0.40-0.98] p=0.036 and OR 0.58 [0.36-0.92] p=0.02, respectively). The lack of association with RA was shown for polymorphic loci of the IL6 (rs1800795), IL6R (rs2228145 and rs4l45618), SLC7A11 (rs13128867), AGER (rs1035798), PTPN2 (rs2542151) and TRAF1/C5 (rs3761847) genes. For RA subsets stratified according to presence/absence of the C. trachomatis/C. pneumoniae infection it was shown that CC genotype at the rs1800795 locus of the IL6 gene and AA genotype at the rs11249215 locus of the RUNX3 gene were associated specifically with the risk of developing Chlamydia infection-associated RA (OR 5.22 [1.85–14.71] p=0.0024 and 2.63 [1.09-6.35] p=0.037). In addition, TG+GG genotypes at the rs2542151 locus of the PTPN2 gene is also associated with RAChl+ clinical phenotype (2.10 [1.10-3.99] p=0.025). No association with either of disease subtypes was revealed for polymorphic loci RUNX1 (rs9979383), IL6R (rs2228145, rs4845618), AGER (rs1035798), SLC7A11 (rs13128867), TRAF1/C5 (rs3761847).ConclusionThus, the polymorphic variants of STAT4, a key gene of autoimmunity, and PTPN22 gene, that is involved in the JAK/STAT pathway of immune response, increase the RA susceptibility in general cohort for the Belarusian population. At the same time, CC genotype at the rs1800795 of the IL6 gene, its product being central proinflammatory cytokine, and AA at the rs11249215 locus of the RUNX3 gene, that is involved in T-cell initiated immune response, as well as the genotypes TG+GG at the rs2542151 locus of the PTPN2 gene, involved in signaling pathways of immune response through T-cell activation, are associated only with RAChl+ clinical phenotype. Our data may indicate that genetic variants of STAT4 and PTPN22 contribute to genetic basis of the pathogenesis of RA through renewal of T-cell initiated immune response.AcknowledgementsThis research was supported by The Research Technical Program “DNA Identification” (2017–2021), project number: 6.4Disclosure of InterestsNone declared