Table1_Exploring the roles and potential therapeutic strategies of inflammation and metabolism in the pathogenesis of vitiligo: a mendelian randomization and bioinformatics-based investigation.XLSX

Introduction:Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism’s pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets.Methods:Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed.Results:MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol’s binding to IRF3, indicating a stable interaction.Conclusion:This study comprehensively elucidates inflammation, immune response, and metabolism’s intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo’s etiology, informing future research and drug development endeavors.

引言：白化病，一种常见的获得性自身免疫性色素性皮肤疾病，由于其病因不明，故而研究颇具挑战。证据表明，炎症和代谢在其发病及进展过程中扮演着关键角色。本研究旨在阐明白化病与炎症蛋白、免疫细胞及代谢物之间的因果关系，探讨双向关联及潜在药物靶点。方法：孟德尔随机化（MR）分析涵盖了4,907种血浆蛋白、91种炎症蛋白、731种免疫细胞特征和1,400种代谢物。生物信息学分析包括蛋白质-蛋白质相互作用（PPI）网络构建、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析。子网络发现和核心蛋白识别采用了分子复杂度检测（MCODE）插件。共定位分析和药物靶点探索，包括分子对接验证，均得以实施。结果：MR分析确定了与白化病相关的49种蛋白、39种免疫细胞特征和59种代谢物。生物信息学分析揭示了其在PPI、GO富集和KEGG通路中的显著作用。子网络分析确定了六个核心蛋白，其中干扰素调节因子3（IRF3）显示出强烈的共定位证据。分子对接验证了白藜芦醇与IRF3的结合，表明其相互作用稳定。结论：本研究全面阐释了炎症、免疫反应和代谢在白化病发病机制中的复杂作用。所识别的蛋白和通路为潜在的治疗靶点，其中IRF3成为一项有希望的候选者。这些发现深化了我们对白化病病因学的理解，为未来的研究和药物开发提供了信息。