鉴定非酒精性脂肪性肝病与心房颤动之间病理生理关联的相关基因和关键途径。
Identification of genes and key pathways underlying the pathophysiological association between nonalcoholic fatty liver disease and atrial fibrillation.
机构信息
Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310006, Zhejiang, China.
出版信息
BMC Med Genomics. 2022 Jul 5;15(1):150. doi: 10.1186/s12920-022-01300-1.
BACKGROUND
Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases.
MATERIALS AND METHODS
NAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein-protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model.
RESULTS
A total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2, PTPRC, CXCR2, MNDA, S100A9, NCF2, S100A12, and S100A8.
CONCLUSIONS
In summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.
背景
心房颤动（AF）是最常见的持续性心律失常之一。最新研究表明，非酒精性脂肪性肝病（NAFLD）与 AF 之间存在紧密关联。然而，NAFLD 与 AF 之间关联的确切分子机制尚不清楚。目前的研究旨在阐述与这两种疾病相关的基因和信号通路。
材料和方法
通过对基因表达综合数据库（GEO）数据集 GSE63067 和 GSE79768 中 NAFLD 和 AF 相关差异表达基因（DEGs）进行生物信息学分析，分别鉴定出与这两种疾病相关的 DEGs。进一步进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析、构建蛋白质-蛋白质相互作用（PPI）网络、识别显著枢纽基因，并进行接收者操作特征曲线分析。利用比较毒理学基因组数据库分析基因-疾病相互作用。此外，通过 NAFLD 细胞模型中的定量实时 PCR（qRT-PCR）验证枢纽基因。
结果
在 NAFLD/AF 与健康对照组个体之间共鉴定出 45 个共表达差异表达基因（co-DEGs）。GO 和 KEGG 通路分析表明，这些 co-DEGs 主要富集于涉及免疫反应和细胞因子-细胞因子受体相互作用的中性粒细胞激活。此外，由于这两个数据集均上调且连通性高，选择了 8 个枢纽基因。这些基因包括 CCR2、PTPRC、CXCR2、MNDA、S100A9、NCF2、S100A12 和 S100A8。
结论
总之，我们对 AF 和 NAFLD 中的 DEG 进行了基因差异表达分析、功能富集分析和 PPI 分析，为 AF 和 NAFLD 中潜在生物标志物的鉴定和有价值的治疗靶点提供了新的见解。
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