Liu, Yang-Lin; Reeves, Helen L; Burt, Alastair D; Tiniakos, Dina; McPherson, Stuart; Leathart, Julian B S; Allison, Michael E D; Alexander, Graeme J; Piguet, Anne Christine; Anty, Rodolphe; Donaldson, Peter; Aithal, Guruprasad P; Francque, Sven; Van Gaal, Luc; Clement, Karine; Ratziu, Vlad; Dufour, Jean-François; Day, Christopher P; Daly, Ann K and Anstee, Quentin M (2014). TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nature communications, 5(4309), p. 4309. Nature Publishing Group 10.1038/ncomms5309
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TM6SF2 rs58542926 influences hepatic fibrosis.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (140kB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie |
UniBE Contributor: |
Piguet, Anne Christine, Dufour, Jean-François |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Lilian Karin Smith-Wirth |
Date Deposited: |
22 Apr 2015 07:58 |
Last Modified: |
05 Dec 2022 14:45 |
Publisher DOI: |
10.1038/ncomms5309 |
PubMed ID: |
24978903 |
BORIS DOI: |
10.7892/boris.67138 |
URI: |
https://boris.unibe.ch/id/eprint/67138 |
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