Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization

Introduction: Behcet's syndrome, as a vasculitic disease involving multiple systems, often induces oral mucosal ulcers. However, levels of inflammatory cytokines and metabolites are unknown for the probability of developing the disease. This study aims to reveal the causal relationship between the cytokines and metabolites and Behcet's syndrome through Mendelian randomization analysis.

Materials and methods: The instrumental variable single nucleotide polymorphisms (SNPs) were used in the study, which showed associations between 91 cytokines and 553 metabolites, respectively. To explore the causal relationship between these exposure factors and Behcet's syndrome, the random effects inverse variance weighting method was adopted. In addition, sensitivity analysis was carried out using Cochran's Q test, heterogeneity test, horizontal pleotropy test and MR-Egger intercept test to evaluate the robustness and validity of our research results.

Results: A total of five substances were identified as causally related to Behcet's syndrome, namely, the cellular factors Interleukin 12 subunit beta(IL-12B) and Interleukin-33(IL-33), the metabolite mannitol, X-12728, and Ratio of Bisallylic groups to double bonds. Furthermore, no significant evidence suggesting heterogeneity or pleiotropy was observed.

Conclusion: Our study adds to current knowledge on the role of specific inflammatory cytokines and metabolites in aetiology of Behcet's syndrome. The identified cytokines and metabolites might be used as markers for clinical screening and prevention of Behcet's syndrome, as well as candidate molecules for future mechanism exploration and drug target selection. Further validation is needed to assess the potential of these cytokines and metabolites as pharmacological targets for Behcet's syndrome prevention.