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DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease

Lookup NU author(s): Dr Mujdat Zeybel, Dr Timothy Hardy, Gemma Zeybel, Dr Matthew BashtonORCiD, Professor John Mathers, Professor Jelena Mann



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


Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B.RESULTS: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium BeadArrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies.CONCLUSIONS: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. CpG methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.

Publication metadata

Author(s): Zeybel M, Vatansever S, Hardy T, Sari AA, Cakalagaoglu F, Avci A, Zeybel GL, Karahüseyinoglu S, Bashton M, Mathers JC, Ünsal B, Mann J

Publication type: Article

Publication status: Published

Journal: Clinical Epigenetics

Year: 2016

Volume: 8

Issue: 48

Pages: 1-10

Online publication date: 05/05/2016

Acceptance date: 28/04/2016

Date deposited: 24/05/2016

ISSN (print): 1868-7075

ISSN (electronic): 1868-7083

Publisher: BioMed Central Ltd.


DOI: 10.1186/s13148-016-0218-1

PubMed id: 27152124


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