Update on genetics and epigenetics in metabolic associated fatty liver disease

Xiaopeng Zhu; Mingfeng Xia; Xin Gao

doi:10.1177/20420188221132138

Update on genetics and epigenetics in metabolic associated fatty liver disease

Ther Adv Endocrinol Metab. 2022 Oct 28:13:20420188221132138. doi: 10.1177/20420188221132138. eCollection 2022.

Authors

Xiaopeng Zhu¹, Mingfeng Xia², Xin Gao¹

Affiliations

¹ Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, Shanghai, China.
² Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is becoming the most frequent chronic liver disease worldwide. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is suggested to replace the nomenclature of NAFLD. For individuals with metabolic dysfunction, multiple NAFLD-related factors also contribute to the development and progression of MAFLD including genetics and epigenetics. The application of genome-wide association study (GWAS) and exome-wide association study (EWAS) uncovers single-nucleotide polymorphisms (SNPs) in MAFLD. In addition to the classic SNPs in PNPLA3, TM6SF2, and GCKR, some new SNPs have been found recently to contribute to the pathogenesis of liver steatosis. Epigenetic factors involving DNA methylation, histone modifications, non-coding RNAs regulations, and RNA methylation also play a critical role in MAFLD. DNA methylation is the most reported epigenetic modification. Developing a non-invasion biomarker to distinguish metabolic steatohepatitis (MASH) or liver fibrosis is ongoing. In this review, we summarized and discussed the latest progress in genetic and epigenetic factors of NAFLD/MAFLD, in order to provide potential clues for MAFLD treatment.

Keywords: GWAS; MAFLD; epigenetics; genetics.

Publication types

Review