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REVIEW article
Front. Physiol.
Sec. Gastrointestinal Sciences
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1562848
This article is part of the Research Topic (Epi)Genetic Alterations and Their Physiological Consequences in Metabolic Dysfunction-associated Steatotic Liver Disease: A Crucial Step Towards Precision Medicine in MASLD View all 3 articles
Role of genetic variants and DNA methylation of lipid metabolism-related genes in metabolic dysfunctionassociated steatotic liver disease
Provisionally accepted- 1 Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Department of Basic Medicine, Gannan Medical University, Ganzhou, China
- 2 Department of Publication Health and Health Management, Gannan Medical University, Ganzhou, China
Metabolic dysfunction-associated steatotic liver disease (MASLD), is one of the most common chronic liver diseases, which encompasses a spectrum of diseases, from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunctionassociated steatohepatitis (MASH), and may ultimately progress to MASH-related cirrhosis and hepatocellular carcinoma (HCC). MASLD is a complex disease that is influenced by genetic and environmental factors. Dysregulation of hepatic lipid metabolism plays a crucial role in the development and progression of MASLD.Therefore, the focus of this review is to discuss the links between the genetic variants and DNA methylation of lipid metabolism-related genes and MASLD pathogenesis. We first summarize the interplay between MASLD and the disturbance of hepatic lipid metabolism. Next, we focus on reviewing the role of hepatic lipid related gene loci in the onset and progression of MASLD. We summarize the existing literature around the single nucleotide polymorphisms (SNPs) associated with MASLD identified by genome-wide association studies (GWAS) and candidate gene analyses. Moreover, based on recent evidence from human and animal studies, we further discussed the regulatory function and associated mechanisms of changes in DNA methylation levels in the occurrence and progression of MASLD, with a particular emphasis on its regulatory role of lipid metabolism-related genes in MASLD and MASH. Furthermore, we review the alterations of hepatic DNA and blood DNA methylation levels associated with lipid metabolism-related genes in MASLD and MASH patients. Finally, we introduce potential value of the genetic variants and DNA methylation profiles of lipid metabolism-related genes in developing novel prognostic biomarkers and therapeutic targets for MASLD, intending to provide references for the future studies of MASLD.
Keywords: metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), Genetic variant, DNA Methylation, Lipid Metabolism, biomarker
Received: 18 Jan 2025; Accepted: 25 Feb 2025.
Copyright: © 2025 Wang, Chen, Zhang, Shen, Zhu, Zhang and Zhang. 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:
Junjie Zhang, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Department of Basic Medicine, Gannan Medical University, Ganzhou, China
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