慢性自发性荨麻疹（CSU）是一种由肥大细胞驱动的疾病，对生活质量有显著影响。虽然遗传因素会影响CSU的易感性和严重程度，但与CSU中肥大细胞活化相关的具体遗传因素尚不明确。我们旨在鉴定关键遗传因素并探究其在CSU发病机制中的作用。通过合并和验证来自基因表达测序数据库的两个基因表达数据集，使用主成分分析和箱线图进行验证。合并后的数据集进行了limma和加权基因共表达网络分析。鉴定出与CSU高度相关的基因，并使用基因集富集分析（GSEA）、基因本体（GO）和基因组百科全书（KEGG）进行分析。由于GSEA、GO和KEGG分析突出显示了趋化因子（C-C基序）配体2（CCL2）和胆固醇25-羟化酶（CH25H）基因以及肿瘤坏死因子（TNF）信号通路在CSU中的重要性，因此在人类肥大细胞系1（HMC-1）中敲除了这三个相应的基因，并与凝血酶共培养，以模拟CSU发病机制。CCL2、CH25H和TNF的敲除减少了HMC-1中的兴奋性和细胞因子产生。我们的研究结果表明CCL2、CH25H和TNF信号通路中的基因在CSU的发病机制中起着至关重要的作用，为CSU治疗的潜在治疗靶点提供了见解。Copyright © 2023 Fang，Weng和Zheng。

Chronic spontaneous urticaria (CSU), a mast cell-driven disease, substantially affects the quality of life. While genetics affect CSU susceptibility and severity, the specific genetic factors associated with mast cell activation in CSU remain elusive. We aimed to identify key genetic factors and investigate their roles in CSU pathogenesis. Two gene expression datasets from the Gene Expression Omnibus were merged and validated using principal component analysis and boxplots. The merged dataset was subjected to limma and weighted gene co-expression network analyses. Genes whose expression correlated highly with CSU were identified and analyzed using Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. As GSEA, GO, and KEGG analyses highlighted the importance of chemokine (C-C motif) ligand 2 (CCL2) and cholesterol 25-hydroxylase (CH25H) gene and tumor necrosis factor (TNF) signaling pathways in CSU; the three corresponding genes were knocked down in human mast cell line-1 (HMC-1), followed by incubation with thrombin to mimic CSU pathogenesis. CCL2, CH25H, and TNF knockdown reduced excitability and cytokine production in HMC-1. Our findings suggest that genes involved in the CCL2, CH25H, and TNF pathways play crucial roles in CSU pathogenesis, providing insights into potential therapeutic targets for CSU treatment.Copyright © 2023 Fang, Weng and Zheng.