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Review
. 2021 Aug:50:101111.
doi: 10.1016/j.molmet.2020.101111. Epub 2020 Nov 5.

Genetic and epigenetic factors determining NAFLD risk

Wenke Jonas  1 , Annette Schürmann  2
Affiliations
Review

Genetic and epigenetic factors determining NAFLD risk

Wenke Jonas et al. Mol Metab. 2021 Aug.

Abstract

Background: Hepatic steatosis is a common chronic liver disease that can progress into more severe stages of NAFLD or promote the development of life-threatening secondary diseases for some of those affected. These include the liver itself (nonalcoholic steatohepatitis or NASH; fibrosis and cirrhosis, and hepatocellular carcinoma) or other organs such as the vessels and the heart (cardiovascular disease) or the islets of Langerhans (type 2 diabetes). In addition to elevated caloric intake and a sedentary lifestyle, genetic and epigenetic predisposition contribute to the development of NAFLD and the secondary diseases.

Scope of review: We present data from genome-wide association studies (GWAS) and functional studies in rodents which describe polymorphisms identified in genes relevant for the disease as well as changes caused by altered DNA methylation and gene regulation via specific miRNAs. The review also provides information on the current status of the use of genetic and epigenetic factors as risk markers.

Major conclusion: With our overview we provide an insight into the genetic and epigenetic landscape of NAFLD and argue about the applicability of currently defined risk scores for risk stratification and conclude that further efforts are needed to make the scores more usable and meaningful.

Keywords: Epigenetics; Genetic variants; NAFLD; Risk score.

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Figures

Figure 1
Figure 1
Frequent gene variants associated with NAFL and/or NASH and their major effects. CPT1, carnitine palmitoyl transferase-1; LPI, lysophosphatidylinositol; PI, phosphatidylinositol.
Figure 2
Figure 2
Summary of the most relevant miRNAs and their targets in the liver and those detected in the plasma of NAFL and NASH patients.
See this image and copyright information in PMC

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