Differentially methylated loci in NAFLD cirrhosis are associated with key signaling pathways

Clinical Epigenetics
Glenn S GerhardJohanna K DiStefano

Abstract

Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip to analyze genome-wide methylation in patients with biopsy-proven grade 3/4 NAFLD fibrosis/cirrhosis (N = 14) and age- and sex-matched controls with normal histology (N = 15). We identified 208 CpG islands (CGIs), including 99 hypomethylated and 109 hypermethylated CGIs, showing statistically significant evidence (adjusted P value < 0.05) for differential methylation between cirrhotic and normal samples. Comparison of β values for each CGI to the read count of its corresponding gene obtained from RNA-sequencing analysis revealed negative correlation (adjusted P value < 0.05) for 34 transcripts. These findings provide supporting evidence for a role for CpG methylation in the pathogenesis of NAFLD-related cirrhosis, including confirmation of previously reported differentially methylated CGIs, and contribute new insight into the molecular mechanisms underlying the initiation and progression of liver fibrosis and cirrh...Continue Reading

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Citations

Sep 8, 2020·Expert Review of Gastroenterology & Hepatology·Letícia F RamosKaren C M Moraes
Aug 21, 2019·Frontiers in Endocrinology·Ebe D'AdamoValerio Nobili
Jun 2, 2020·World Journal of Gastroenterology : WJG·Feng-Zhi XinJian-Gao Fan
Jan 2, 2020·Clinical Epigenetics·Madelon L GeurtsenJanine F Felix
Nov 17, 2020·Frontiers in Genetics·Shaza AsifKyoung-Han Kim
Apr 4, 2021·Cancers·María ArechederraCarmen Berasain
Aug 7, 2021·Clinical Epigenetics·Nicholas D JohnsonJohanna K DiStefano
Aug 28, 2021·Cancers·Ewa Wolinska, Maciej Skrzypczak

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Methods Mentioned

BETA
biopsies
methylation
Assay
RNA-Seq
biopsy
gastric

Software Mentioned

Bowtie
DESeq2
minfi
minfi R package
Ingenuity Pathway Analysis ( IPA )
Cufflinks
CpGassoc

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