Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2015; 21(39): 11088-11111
Published online Oct 21, 2015. doi: 10.3748/wjg.v21.i39.11088
Genetic background in nonalcoholic fatty liver disease: A comprehensive review
Fabio Salvatore Macaluso, Marcello Maida, Salvatore Petta
Fabio Salvatore Macaluso, Marcello Maida, Salvatore Petta, Section of Gastroenterology, DIBIMIS, University of Palermo, 90127 Palermo, Italy
Author contributions: All authors contributed to writing the paper and had full control over preparation of manuscript; all authors approved the final draft manuscript.
Conflict-of-interest statement: No conflict-of-interest exists.
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: Fabio Salvatore Macaluso, MD, Section of Gastroenterology, DIBIMIS, University of Palermo, Piazza delle Cliniche 2, 90127 Palermo, Italy. fsmacaluso@gmail.com
Telephone: +39-91-6552274 Fax: +39-91-6552156
Received: April 23, 2015
Peer-review started: April 24, 2015
First decision: June 2, 2015
Revised: June 11, 2015
Accepted: September 2, 2015
Article in press: September 2, 2015
Published online: October 21, 2015
Abstract

In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.

Keywords: Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, Genetics, Genome-wide association studies, Patatin-like phospholipase domain-containing 3, Transmembrane 6 superfamily member 2, Candidate gene studies

Core tip: Nonalcoholic fatty liver disease (NAFLD) is regarded as the most significant liver disease from the twenty-first century in the Western world. Although its development is surely driven by environmental factors, it is also regulated by genetic background. The role of heritability has been widely demonstrated by several studies, likely reflecting the diverse genetic variability in systemic metabolism and wound healing response processes. Accordingly, we performed a review of the literature on the role of genetics in NAFLD and outlined here the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.