NAFLD: genetics and its clinical implications

Abstract

Worldwide non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of liver disease and its burden increasing at an alarming rate. NAFLD entails steatosis, fibrosis, cirrhosis, and, finally, hepatocellular carcinoma (HCC). The substantial inter-patient variation during disease progression is the hallmark of individuals with NAFLD. The variability of NAFLD development and related complications among individuals is determined by genetic and environmental factors. Genome-wide association studies (GWAS) have discovered reproducible and robust associations between gene variants such as PNPLA3, TM6SF2, HSD17B13, MBOAT7, GCKR and NAFLD. Evidences have provided the new insights into the NAFLD biology and underlined potential pharmaceutical targets. Ideally, the candidate genes associated with the hereditability of NAFLD are mainly involved in assembly of lipid droplets, lipid remodeling, lipoprotein packing and secretion, redox status mitochondria, and de novo lipogenesis. In recent years, the ability to translate genetics into a clinical context has emerged substantially by combining genetic variants primarily associated with NAFLD into polygenic risk scores (PRS). These score in combination with metabolic factors could be utilized to identify the severe liver diseases in patients with the gene regulatory networks (GRNs). Hereby, we even have highlighted the current understanding related to the schedule therapeutic approach of an individual based on microbial colonization and dysbiosis reversal as a therapy for NAFLD. The premise of this review is to concentrate on the potential of genetic factors and their translation into the design of novel therapeutics, as well as their implications for future research into personalized medications using microbiota.

Keywords: Non-alcoholic fatty liver disease; PNPLA3 gene; Personalized therapeutics; Polymorphism; Risk assessment; Steatohepatitis.