Association between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis susceptibility: a meta-analysis and trial sequential analysis

Objective This meta-analysis was conducted to investigate the relationship between the interleukin (IL)-17A rs2275913 polymorphism and rheumatoid arthritis (RA) susceptibility. Methods Eligible studies were retrieved from PubMed, Embase, and Web of Science. The fixed- or random-effects model was used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) on the basis of heterogeneity. Results Overall, 11 studies containing 4019 RA patients and 4137 controls were included in this meta-analysis. The results suggested a significant association between the IL-17A rs2275913 polymorphism and RA susceptibility in the overall population (allelic model A vs. G: OR = 0.89, 95%CI: 0.83–0.95; heterozygote model GA vs. GG: OR = 0.87, 95%CI: 0.78–0.96; homozygote model AA vs. GG: OR = 0.82, 95%CI: 0.71–0.96; dominant model GA + AA vs. GG: OR = 0.86, 95%CI: 0.78–0.94). In the subgroup analyses, the IL-17A rs2275913 polymorphism was significantly associated with RA risk in Europeans (allelic model A vs. G: OR = 0.87, 95%CI: 0.78–0.97; heterozygote model GA vs. GG: OR = 0.79, 95%CI: 0.68–0.93; dominant model GA + AA vs. GG: OR = 0.79, 95%CI: 0.68–0.92), but not in Africans or Americans. Conclusion This study suggests that the IL-17A rs2275913 polymorphism is significantly associated with RA susceptibility in Europeans. INPLASY registration number: INPLASY202170056.

AB0008 THE IMPACT OF STAT4 RS7574865, IL6 RS1800795, IL6R RS2228145 AND RS4845618 ON RHEUMATOID ARTHRITIS SUSCEPTIBILITY IN BELARUSIAN POPULATION

Background:Rheumatoid arthritis (RA) is a chronic systemic disorder of the connective tissue of still unknown aetiology and complex autoimmune pathogenesis that primarily affects small joints. HLA alleles provide for 11-37% of the RA heritability, suggesting the substantial role of the non-HLA loci in genetic predisposition to RA. Among non-HLA loci,IL6, IL6RandSTAT4genes attract attention, however, the data concerning their influence on RA risk are somewhat contradictory.Objectives:The aim of the study was to analyze the involvement of four SNPs (STAT4rs7574865,IL6rs1800795,IL6Rrs2228145 and rs4845618) in RA susceptibility.Methods:187 patients diagnosed with RA (mean age 58.2 ± 11.9), and 380 healthy blood donors (mean age 37.18 ± 10.69 years) were included into the study. DNA extraction from peripheral blood samples was performed using the phenol-chloroform method. SNPs were genotyped using the real-time PCR with fluorescent probes. The allele and genotype frequencies were compared using the χ2 test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the VassarStats online tool.Results:Utilizing recessive genetic model we found an association between TT genotype ofSTAT4rs7574865 (OR = 2.362; 95%CI [1.0378 – 5.376], p = 0.038) and RA. ForIL6rs1800795, it was found that CC genotype had significantly higher frequency among patients with rheumatoid arthritis as compared to that in controls (OR = 1.52; 95%CI [1.02 – 2.27], p = 0.0456). No associations ofIL6Rrs2228145 and rs4845618 SNPs with risk of RA were found in the total group of patients vs. controls. It was also shown thatIL6rs1800795 CC genotype frequency was significantly higher among the patients with RF-negative status (p = 0.0019).Conclusion:Thus, we provide evidence for association of theSTAT4rs7574865 andIL6rs1800795 variants with risk of RA in the Belarusian population, some features of interplay being revealed between gene polymorphisms analyzed and RA antibody status. Abovementioned SNPs may contribute to RA genetic susceptibility in the Belarusian population.Disclosure of Interests:None declared

IL-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility

Interleukin-21 (IL-21) is a cytokine that plays a crucial role in pathogenesis and activity of the rheumatoid arthritis (RA). Meanwhile, genetic polymorphisms in the IL-21 gene may alter its expression. Previous studies have reported conflicting results assessing the association between the IL-21 rs6822844 G/T polymorphism and RA risk. Thus, it’s necessary to perform a meta-analysis to definite above relationship. PubMed database was searched for all papers published until October 20, 2019. Nine case–control studies with 9998 cases and 10742 controls were retrieved based on the search criteria at last. Odds ratio (95% confidence interval) was used to calculate the strength of this association. Publication bias was detected using both Begg’s and Egger’s tests. Overall, the IL-21 rs6822844 G/T polymorphism was found to be significantly associated with decreased RA risk (e.g. T-allele versus G-allele: OR = 0.81, 95% CI = 0.72–0.91, P < 0.001). In addition, decreased RA risk was also detected both in Asians (eg: TT+TG versus GG: OR = 0.42, 95% CI = 0.31–0.56, P < 0.001) and Caucasians (eg: TT+TG versus GG: OR = 0.85, 95% CI = 0.80–0.91, P < 0.001). A similar trend in association was found in the source of the control and genotype method subgroups. Furthermore, subgroup analysis of rheumatoid factor status revealed a protective relationship between the IL-21 rs6822844 G/T polymorphism and RF+/RF- RA risk. A similar relationship was noted in the anti-citrullinated protein antibody status subgroup. The results of the present study suggest that the IL-21 rs6822844 G/T polymorphism was significantly associated with decreased RA susceptibility.