Scholarlink

<p>Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD (non-alcoholic fatty liver disease), is a growing global concern, affecting nearly a third of the world’s population. This umbrella term covers a range of liver pathologies, from reversible disease stages like simple steatosis, to irreversible conditions such as cirrhosis and hepatocellular carcinoma (HCC). MASLD, which may result from metabolic risk factors like obesity and type 2 diabetes, is projected to increase due to a rise in sedentary lifestyles. This review addresses genetic influences that predispose to disease development, including the role of risk-conferring and protective/preventive alleles. The epistatic relationships between genetic variants can significantly influence the development and progression of MASLD. Key genetic variants, such as those located in the <i>PNPLA3</i>, <i>TM6SF2</i>, and <i>MBOAT7</i> genes, often interact to exacerbate MASLD severity and play key roles in lipid metabolism and liver inflammation. For example, the co-expression of certain <i>PNPLA3</i> and <i>TM6SF2</i> variants increases the risk of advanced fibrosis and HCC. Some variants located in <i>HSD17B13</i> and <i>MTARC1</i> offer protective effects, reducing the risk of severe liver disease despite comorbidities such as obesity, and can mitigate the harmful effects of these risk alleles. Additionally, the potential of polygenic risk scores (PRS) to predict MASLD development and its complications is also discussed, although challenges remain, particularly in underrepresented populations due to the lack of comprehensive catalogues of genetic variation. Understanding these complex gene-gene interactions and the role of the environment underscores the importance of considering epistatic relationships when assessing MASLD risk and developing personalized therapeutic strategies, which could ease the future burden on healthcare systems.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genetic modulators of metabolic dysfunction-associated steatotic liver disease (MASLD) and their epistatic interactions: from in vitro and animal models to clinical outcomes

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月2日

查看全文
  • Fernanda G. Arriaga-González,
  • Felipe de Jesús Castañeda-Córdova,
  • Mauricio Díaz-Muñoz,
  • Matthew Hoare,
  • David J. Adams,
  • Carla Daniela Robles-Espinoza,
  • Christian Molina-Aguilar

摘要

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as NAFLD (non-alcoholic fatty liver disease), is a growing global concern, affecting nearly a third of the world’s population. This umbrella term covers a range of liver pathologies, from reversible disease stages like simple steatosis, to irreversible conditions such as cirrhosis and hepatocellular carcinoma (HCC). MASLD, which may result from metabolic risk factors like obesity and type 2 diabetes, is projected to increase due to a rise in sedentary lifestyles. This review addresses genetic influences that predispose to disease development, including the role of risk-conferring and protective/preventive alleles. The epistatic relationships between genetic variants can significantly influence the development and progression of MASLD. Key genetic variants, such as those located in the PNPLA3, TM6SF2, and MBOAT7 genes, often interact to exacerbate MASLD severity and play key roles in lipid metabolism and liver inflammation. For example, the co-expression of certain PNPLA3 and TM6SF2 variants increases the risk of advanced fibrosis and HCC. Some variants located in HSD17B13 and MTARC1 offer protective effects, reducing the risk of severe liver disease despite comorbidities such as obesity, and can mitigate the harmful effects of these risk alleles. Additionally, the potential of polygenic risk scores (PRS) to predict MASLD development and its complications is also discussed, although challenges remain, particularly in underrepresented populations due to the lack of comprehensive catalogues of genetic variation. Understanding these complex gene-gene interactions and the role of the environment underscores the importance of considering epistatic relationships when assessing MASLD risk and developing personalized therapeutic strategies, which could ease the future burden on healthcare systems.