DNA methylation profile of liver tissue in end-stage cholestatic liver disease

Angela C. Cheung; Brian D. Juran; Erik M. Schlicht; Bryan M. McCauley; Elizabeth J. Atkinson; Raymond Moore; Julie K. Heimbach; Kymberly D. Watt; Tsung Teh Wu; Nicholas F. Larusso; Gregory J. Gores; Zhifu Sun; Konstantinos N. Lazaridis

doi:10.2217/epi-2021-0343

DNA methylation profile of liver tissue in end-stage cholestatic liver disease

Angela C. Cheung, Brian D. Juran, Erik M. Schlicht, Bryan M. McCauley, Elizabeth J. Atkinson, Raymond Moore, Julie K. Heimbach, Kymberly D. Watt, Tsung Teh Wu, Nicholas F. Larusso, Gregory J. Gores, Zhifu Sun, Konstantinos N. Lazaridis

Research output: Contribution to journal › Article › peer-review

Abstract

Aims: In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes. Patients methods: Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.

Original language	English (US)
Pages (from-to)	481-497
Number of pages	17
Journal	Epigenomics
Volume	14
Issue number	8
DOIs	https://doi.org/10.2217/epi-2021-0343
State	Published - Apr 2022

Keywords

DNA methylation
alcoholic liver disease
alcoholic steatohepatitis
cirrhosis
differentially methylated regions
epigenetic
methylome
primary biliary cholangitis
primary biliary cirrhosis
primary sclerosing cholangitis

ASJC Scopus subject areas

Genetics
Cancer Research

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title = "DNA methylation profile of liver tissue in end-stage cholestatic liver disease",

abstract = "Aims: In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes. Patients methods: Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.",

keywords = "DNA methylation, alcoholic liver disease, alcoholic steatohepatitis, cirrhosis, differentially methylated regions, epigenetic, methylome, primary biliary cholangitis, primary biliary cirrhosis, primary sclerosing cholangitis",

author = "Cheung, {Angela C.} and Juran, {Brian D.} and Schlicht, {Erik M.} and McCauley, {Bryan M.} and Atkinson, {Elizabeth J.} and Raymond Moore and Heimbach, {Julie K.} and Watt, {Kymberly D.} and Wu, {Tsung Teh} and Larusso, {Nicholas F.} and Gores, {Gregory J.} and Zhifu Sun and Lazaridis, {Konstantinos N.}",

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year = "2022",

month = apr,

doi = "10.2217/epi-2021-0343",

language = "English (US)",

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AU - Cheung, Angela C.

AU - Juran, Brian D.

AU - Schlicht, Erik M.

AU - McCauley, Bryan M.

AU - Atkinson, Elizabeth J.

AU - Moore, Raymond

AU - Heimbach, Julie K.

AU - Watt, Kymberly D.

AU - Wu, Tsung Teh

AU - Larusso, Nicholas F.

AU - Gores, Gregory J.

AU - Sun, Zhifu

AU - Lazaridis, Konstantinos N.

PY - 2022/4

Y1 - 2022/4

N2 - Aims: In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes. Patients methods: Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.

AB - Aims: In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes. Patients methods: Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.

KW - DNA methylation

KW - alcoholic liver disease

KW - alcoholic steatohepatitis

KW - cirrhosis

KW - differentially methylated regions

KW - epigenetic

KW - methylome

KW - primary biliary cholangitis

KW - primary biliary cirrhosis

KW - primary sclerosing cholangitis

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DNA methylation profile of liver tissue in end-stage cholestatic liver disease

Abstract

Keywords

ASJC Scopus subject areas

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