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

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 cirrhosis.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Gerhard GS,Malenica I,Llaci L,Chu X,Petrick AT,Still CD,DiStefano JK

doi

10.1186/s13148-018-0525-9

subject

Has Abstract

pub_date

2018-07-13 00:00:00

pages

93

issue

1

eissn

1868-7075

issn

1868-7083

pii

10.1186/s13148-018-0525-9

journal_volume

10

pub_type

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