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Differential DNA methylation of genes involved in fibrosis progression in non-alcoholic fatty liver disease and alcoholic liver disease

Lookup NU author(s): Dr Mujdat Zeybel, Dr Timothy Hardy, Stuart Robinson, Christopher Fox, Professor Quentin Anstee, Dr Steven Masson, Professor John Mathers, Jeremy French, Steven White, Professor Jelena Mann

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


Abstract

Background: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patients. Currently, it is not clear which factors determine progression to fibrosis. We investigated whether DNA\methylation profile as determined by pyrosequencing can distinguish patients with mild from those with advanced/severe fibrosis in non-alcoholic liver disease (NAFLD) and alcoholic liver disease (ALD). To this end, paraffin-embedded liver biopsies were collected from patients with biopsy-proven NAFLD or ALD, as well as paraffin-embedded normal liver resections, genomic DNA isolated, bisulfite converted and pyrosequencing assays used to quantify DNA methylation at specific CpGs within PPAR alpha, PPAR alpha, TGF beta 1, Collagen 1A1 and PDGF alpha genes. Furthermore, we assessed the impact of age, gender and anatomical location within the liver on patterns of DNA methylation in the same panel of genes.Results: DNA methylation at specific CpGs within genes known to affect fibrogenesis distinguishes between patients with mild from those with severe fibrosis in both NAFLD and ALD, although same CpGs are not equally represented in both etiologies. In normal liver, age, gender or anatomical location had no significant impact on DNA methylation patterns in the liver.Conclusions: DNA methylation status at specific CpGs may be useful as part of a wider set of patient data for predicting progression to liver fibrosis.


Publication metadata

Author(s): Zeybel M, Hardy T, Robinson SM, Fox C, Anstee QM, Ness T, Masson S, Mathers JC, French J, White S, Mann J

Publication type: Article

Publication status: Published

Journal: Clinical Epigenetics

Year: 2015

Volume: 7

Issue: 25

Online publication date: 14/03/2015

Acceptance date: 10/02/2015

Date deposited: 09/06/2015

ISSN (electronic): 1868-7083

Publisher: BioMed Central Ltd

URL: http://dx.doi.org/10.1186/s13148-015-0056-6

DOI: 10.1186/s13148-015-0056-6


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