POS1489 DECIPHERING THE ASSOCIATION BETWEEN CIRCULATING INTERLEUKINS AND SYSTEMIC LUPUS ERYTHEMATOSUS

Background Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology that can affect various organ systems, particularly the kidneys [1] . Interleukin-6 (IL-6), Interleukin-17 (IL-17), and tumour necrosis factor-α (TNF-α) are closely correlated with risk SLE play a significant role in pathogenesis disease. However, causal relationship between these cytokines has not been elucidated. Objectives Our study aimed to assess association IL-17, IL-6, TNF-α, by Mendelian randomization (MR) study. Methods Data on both were obtained from aggregate-level data publicly available Genome-Wide Association Study (GWAS), Finnish database comprising mainly participants European ancestry [2-3] Bi-directional two-sample MR was performed using inverse variance weighting (IVW), MR-Egger regression weighted median methods. In addition, leave-one-out analyses potential pleiotropy cytokines. Finally, direct relationships IL-6 TNF-α estimated multivariate analysis (MVMR). Results The IVW results MVMR showed IL-17 had developing (95% CI = 0.168~ 1.207, P 0.009). No associations observed (95%CI=-0.610-0.188, P=0.302) as well (95%CI=-0.120~0.178, P=0.707). Evidence bidirectional did support reverse causality. Specifically, follows, (OR=1.017, P=0.081), (OR=1.015, P=0.122), (OR=1.027, P=0.063). Cochran’s Q test there no heterogeneity SNPs IVs. Furthermore, pooled effects corroborated results, suggesting across estimates included SNPs. Conclusion conclusion, present supports hypothesis genetically predicted higher levels circulating directly associated increased SLE. Accordingly, drugs targeting may be highly effective promising therapeutic options. References [1]GC Tsokos. erythematosus. N Engl J Med 2011;365(22):2110-21. [2]AV Ahola-Olli, Wurtz, AS Havulinna, et al. Genome-wide Identifies 27 Loci Influencing Concentrations Circulating Cytokines Growth Factors. Am Hum Genet 2017;100(1):40-50. [3]J Bentham, DL Morris, D Graham, Genetic implicate aberrant regulation innate adaptive immunity genes systemic Nat 2015;47(12):1457-64. Acknowledgements: NIL. Disclosure Interests None Declared.