Genetic and Epigenetic Culprits in the Pathogenesis of Nonalcoholic Fatty Liver Disease

J Clin Exp Hepatol. 2018 Dec;8(4):390-402. doi: 10.1016/j.jceh.2018.04.001. Epub 2018 Apr 25.

Abstract

Nonalcoholic Fatty Liver Disease (NAFLD) constitutes a wide spectrum of liver pathology with hepatic steatosis at the core of this pathogenesis. Variations of certain genetic components have demonstrated increased susceptibility for hepatic steatosis. Therefore, these inciting variants must be further characterized in order to ultimately provide effective, targeted therapies for NAFLD and will be the focus of this review. Several genetic variants revealed an association with NAFLD through Genome-wide Association Study, meta-analyses, and retrospective case-control studies. PNPLA3 rs738409 and TM6SF2 rs58542926 are the two genetic variants providing the strongest evidence for association with NAFLD. However, it remains to be determined if these genetic variants serve as the primary culprit which induces the pathogenesis of NAFLD. Prospective and intervention studies are urgently needed to firmly establish a cause-and-effect relationship between the presence of certain genetic variants and risk of NAFLD development and progression.

Keywords: 1H-MRS, Proton Magnetic Resonance Spectroscopy; ACC2, Acetyl-CoA Carboxylase 2; ACLY, ATP Citrate Lyase; BMI, Body Mass Index; CK-18, Cytokeratin 18; CT, Computed Tomography; FASN, Fatty Acid Synthase; GWAS, Genome-wide Association Study; HCC, Hepatocellular Carcinoma; LT, Liver Transplantation; NAFLD, Nonalcoholic Fatty Liver Disease; NASH, Nonalcoholic Steatohepatitis; SCD1, Stearoyl-CoA Desaturase 1; SNP, Single Nucleotide Polymorphism; US, Ultrasonography; epigenetics; genetic polymorphisms; genetic variants; miRNA, MicroRNA; nonalcoholic fatty liver disease; single nucleotide polymorphisms.

Publication types

  • Review