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TM6SF2 rs58542926 Influences Hepatic Fibrosis Progression in Patients with Non-Alcoholic Fatty Liver Disease

Lookup NU author(s): Dr Yang-Lin Liu, Professor Helen Reeves, Professor Alastair Burt, Dr Dina Tiniakos Tiniakos, Dr Stuart McPherson, Julian Leathart, Rodolphe Anty, Dr Peter Donaldson, Professor Chris Day, Professor Ann Daly, Professor Quentin Anstee

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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

Pages: 1-6

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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