Zheng Wei, Wang Shouhao, Wang Huafang, Xu Chengan, Yin Qiaoqiao, Di Hua
Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
IUBMB Life. 2025 Jul;77(7):e70040. doi: 10.1002/iub.70040.
Nonalcoholic fatty liver disease (NAFLD) is closely associated with coronary artery disease (CAD); however, their shared genetic traits and molecular mechanisms in lipid metabolism remain unclear. In this study, we identified that the differentially expressed genes in NAFLD and CAD intersected with lipid metabolism genes to obtain three key genes-GPD1, MVK, and PIK3R2. Data from the GeneCards database indicated a significant correlation between NAFLD-related regulatory genes and the expression levels of these key genes. Notably, GPD1 showed a significant positive correlation with PNPLA3 (r = 0.715), while PIK3R2 exhibited a significant negative correlation with MIR21 (r = -0.691). Similarly, CAD regulatory genes were significantly correlated with the expression levels of these key genes; GPD1 showed a significant positive correlation with APOA1 (r = 0.751), and PIK3R2 had a significant negative correlation with LPA (r = -0.362). Additionally, single-cell sequencing analysis of NAFLD showed that GPD1, MVK, and PIK3R2 had higher activity in cells with a high expression of bile acid metabolism genes in the immune pathway. In CAD, GPD1 showed higher activity in cells with high oxidative phosphorylation in the immune pathway. Finally, we found that one drug interacted with MVK, while 38 drugs interacted with PIK3R2. This study highlights GPD1, MVK, and PIK3R2 as key genes involved in NAFLD, CAD, and lipid metabolism, suggesting potential targets for further mechanistic studies and novel therapeutic approaches for patients with NAFLD and CAD.
非酒精性脂肪性肝病（NAFLD）与冠状动脉疾病（CAD）密切相关；然而，它们在脂质代谢方面共同的遗传特征和分子机制仍不清楚。在本研究中，我们确定了NAFLD和CAD中差异表达的基因与脂质代谢基因相交，从而获得了三个关键基因——GPD1、MVK和PIK3R2。来自基因卡数据库的数据表明，NAFLD相关调控基因与这些关键基因的表达水平之间存在显著相关性。值得注意的是，GPD1与PNPLA3呈显著正相关（r = 0.715），而PIK3R2与MIR21呈显著负相关（r = -0.691）。同样，CAD调控基因与这些关键基因的表达水平显著相关；GPD1与APOA1呈显著正相关（r = 0.751），PIK3R2与LPA呈显著负相关（r = -0.362）。此外，NAFLD的单细胞测序分析表明，GPD1、MVK和PIK3R2在免疫途径中胆汁酸代谢基因高表达的细胞中具有较高活性。在CAD中，GPD1在免疫途径中氧化磷酸化高的细胞中表现出较高活性。最后，我们发现一种药物与MVK相互作用，而38种药物与PIK3R2相互作用。本研究强调了GPD1、MVK和PIK3R2作为参与NAFLD、CAD和脂质代谢的关键基因，为进一步的机制研究和NAFLD及CAD患者的新治疗方法提供了潜在靶点。
