AB0195 GENETIC ASSOCIATION BETWEEN INTERLEUKIN-17 AND SUSCEPTIBILITY TO RHEUMATOID ARTHRITIS

Abstract

BackgroundThe pathogenesis of rheumatoid arthritis (RA) is immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved[1]. In particular, interleukin-17 (IL-17) is a potent pro-inflammatory cytokine[2], but the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and rheumatoid arthritis remained unknown at genetic.ObjectivesIn this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA.MethodsSummary statistics for RA (14,361 RA cases and 43,923 healthy controls (HCs)) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps (p < 1.0 × 10-5) from the GWAS summary results. Mendelian randomization (MR) analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods. For assessing the robustness of the results, we also carried out sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out and MR pleiotropy residual sum and outlier (MR-PRESSO).ResultsMR Methods were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC and IL-17D/IL-17RD and RA. The result of MR analysis indicated that the higher level of IL-17RA (95%CI = 1.006-1.231, p = 0.038) was associated with a significantly higher risk of RA, while remaining exposure IVs did not show a causal relationship with RA, including IL-17A(95%CI = 0.990-1.210, p = 0.078), IL-17C(95%CI = 0.890-1.139, p = 0.910), IL-17RC(95%CI = 0.904-1.119, p = 0.913), IL-17D(95%CI = 0.843-1.137, p = 0.778), IL-17RD(95%CI = 0.876-1.104, p = 0.773). More importantly, sensitivity analysis showed no heterogeneity or pleiotropy in any of the above results.ConclusionMR analysis supported a potential causal relationship between IL-17RA and the risk of RA, prompting that doctors should pay close attention to the level of IL-17RA during the examination of RA patients. Furthermore, it will promote future studies on reducing the risk of RA by developing drugs that limitation IL-17A.