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ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 15 - 2024 |
doi: 10.3389/fgene.2024.1464865
Identification of novel targets associated with cholesterol metabolism in nonalcoholic fatty liver disease: a comprehensive study using Mendelian randomization combined with transcriptome analysis
Provisionally accepted- 1 Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou, China
- 2 Affiliated Fuzhou First Hospital of Fujian Medical University, Fuzhou, China
- 3 Fujian Provincial Hospital, Fuzhou, China
Background: There is limited research on cholesterol metabolism-related genes (CM-RGs) in non-alcoholic fatty liver disease (NAFLD), despite hypercholesterolemia being a recognized risk factor. The role of CM-RGs in NAFLD remains unclear.The differentially expressed genes (DEGs) between NAFLD and control were acquired by differential expression analysis. The differentially expressed genes associated with cholesterol metabolism (DE-CM-RGs) were identified and functional enrichment analyses were performed. Protein-protein interaction network analysis and a two-sample Mendelian randomization study were utilized for identifying hub genes.Nomogram model, competing endogenous RNA and messenger RNA-drug networks were established. In addition, immunoinfiltration analysis was performed.Results: We identified four hub genes (MVK, HMGCS1, TM7SF2, and FDPS) linked to NAFLD risk. MVK and TM7SF2 were protective factors, HMGCS1 and FDPS were risk factors for NAFLD. The area under the curve values of nomograms in GSE135251 and GSE126848 were 0.79 and 0.848, respectively. The gene set enrichment analysis indicated that hub genes participated in calcium signaling pathways and biosynthesis of unsaturated fatty acids. NAFLD patients showed increased CD56 dim NK cells and Th17. Tretinoin, alendronate, zoledronic acid, and quercetin are potential target agents in NAFLD.Our study has linked cholesterol metabolism genes (MVK, HMGCS1, TM7SF2, and FDPS) to NAFLD, providing a promising diagnostic framework, identifying treatment targets, and offering novel perspectives into its mechanisms.
Keywords: NAFLD, cholesterol metabolism, prognosis, Bioinformatic analysis, Mendelian randomization
Received: 18 Jul 2024; Accepted: 06 Sep 2024.
Copyright: © 2024 Chen, Rao and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaoling Zheng, Fujian Provincial Hospital, Fuzhou, China
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