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https://hdl.handle.net/2440/86427
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Type: | Journal article |
Title: | TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease |
Author: | Liu, Y. Reeves, H. Burt, A. Tiniakos, D. McPherson, S. Leathart, J. Allison, M. Alexander, G. Piguet, A. Anty, R. Donaldson, P. Aithal, G. Francque, S. Van Gaal, L. Clement, K. Ratziu, V. Dufour, J. Day, C. Daly, A. Anstee, Q. |
Citation: | Nature Communications, 2014; 5(1):4309-1-4309-6 |
Publisher: | Nature Publishing Group |
Issue Date: | 2014 |
ISSN: | 2041-1723 2041-1723 |
Statement of Responsibility: | Yang-Lin Liu, Helen L. Reeves, Alastair D. Burt, Dina Tiniakos, Stuart McPherson, Julian B. S. Leathart, Michael E. D. Allison, Graeme J. Alexander, Anne-Christine Piguet, Rodolphe Anty, Peter Donaldson, Guruprasad P. Aithal, Sven Francque, Luc Van Gaal, Karine Clement, Vlad Ratziu, Jean-Francois Dufour, Christopher P. Day, Ann K. Daly, Quentin M. Anstee |
Abstract: | Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that 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 characterized 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 and PNPLA3 rs738409 genotype), with advanced hepatic fibrosis/cirrhosis. These findings establish new and important clinical relevance to TM6SF2 in NAFLD. |
Keywords: | Liver Humans Liver Cirrhosis Disease Progression Genetic Predisposition to Disease Lectins, C-Type Membrane Proteins Nerve Tissue Proteins Cohort Studies Genotype Heterozygote Polymorphism, Single Nucleotide Alleles Adult Aged Middle Aged Female Male Chondroitin Sulfate Proteoglycans Non-alcoholic Fatty Liver Disease |
Rights: | © 2014 Macmillan Publishers Ltd. All rights reserved. This article has been distributed under a Creative Commons CC-BY license (please see the article itself for the license version number). You may reuse this material without obtaining permission from Nature Publishing Group, providing that the author and the original source of publication are fully acknowledged, as per the terms of the license. For license terms, please see http://creativecommons.org/ |
DOI: | 10.1038/ncomms5309 |
Published version: | http://dx.doi.org/10.1038/ncomms5309 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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