Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2016; 22(29): 6742-6756
Published online Aug 7, 2016. doi: 10.3748/wjg.v22.i29.6742
Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review
Tyler J Severson, Siddesh Besur, Herbert L Bonkovsky
Tyler J Severson, Herbert L Bonkovsky, Department of Gastroenterology and Hepatology, Wake Forest University NC Baptist Medical Center, Winston-Salem, NC 27157, United States
Siddesh Besur, Abdominal Transplant Program, Aurora St Luke’s Medical Center, Milwaukee, WI 53215, United States
Author contributions: Bonkovsky HL conceived the topic and developed the initial outline; all authors participated in the literature review and wrote sections of the manuscript; all authors edited and revised the manuscript; Severson TJ identified the figures and adapted the tables.
Conflict-of-interest statement: All authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Herbert L Bonkovsky, MD, Professor, Department of Gastroenterology and Hepatology, Wake Forest University NC Baptist Medical Center, Nutrition Bldg, E-112, 1 Medical Center Blvd, Winston-Salem, NC 27157, United States. hbonkovs@wakehealth.edu
Telephone: +1-336-7137341 Fax: +1-336-7137322
Received: February 10, 2016
Peer-review started: February 10, 2016
First decision: March 7, 2016
Revised: March 28, 2016
Accepted: May 23, 2016
Article in press: May 23, 2016
Published online: August 7, 2016
Processing time: 170 Days and 14.1 Hours
Abstract

AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.

METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.

RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.

CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.

Keywords: Genetic polymorphisms; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; PNPLA3; TM6SF2; FTO; Cirrhosis; Iron metabolism

Core tip: Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions not only in the United States but worldwide. Its end results can include non-alcoholic steatohepatitis, cirrhosis, liver failure, and hepatocellular carcinoma. Studies since 2008 have demonstrated and continue to uncover noteworthy genetic factors that influence NAFLD and its onset, severity, and ultimate outcome. Awareness of these genetic elements yields improved understanding of the pathology of the disease and will likely be key to individualizing effective patient therapy in the near future.