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Lookup NU author(s): Dr Yang-Lin Liu, Professor Helen ReevesORCiD, Professor Alastair BurtORCiD, Dr Dina Tiniakos, Professor Stuart McPhersonORCiD, Julian Leathart, Rodolphe Anty, Dr Peter Donaldson, Professor Chris Day, Professor Ann DalyORCiD, Professor Quentin AnsteeORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, which can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure. Subtle inter-patient genetic variation and environmental factors combine to determine variation in disease progression. A common non-synonymous polymorphism in TM6SF2 (rs58542926 c.449 C>T, p.Glu167Lys) was recently associated with increased hepatic triglyceride content, but whether this variant promotes clinically relevant hepatic fibrosis is unknown. Here we confirm that TM6SF2 minor allele carriage is associated with NAFLD and is causally related to a previously reported chromosome 19 GWAS signal that was ascribed to the gene NCAN. Furthermore, using two histologically characterised cohorts encompassing steatosis, steatohepatitis, fibrosis and cirrhosis (combined n=1,074), we demonstrate a new association, independent of potential confounding factors (age, BMI, type 2 diabetes mellitus, PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD.
Author(s): Liu Y-L, Reeves HL, Burt AD, Tiniakos D, McPherson S, Leathart JBS, Allison MED, Alexander GJ, Piguet A-C, Anty R, Donaldson P, Aithal GP, Francque S, VanGaal L, Clement K, Ratziu V, Dufour J-F, Day CP, Daly AK, Anstee QM
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2014
Volume: 5
Online publication date: 30/06/2014
Acceptance date: 05/06/2014
Date deposited: 01/03/2015
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/ncomms5309
DOI: 10.1038/ncomms5309
PubMed id: 24978903
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