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Series GSE49542 Query DataSets for GSE49542
Status Public on Aug 30, 2013
Title Methylation profiles in non-alcoholic fatty liver disease
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression.

Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome.

Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed.

Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD.

Overall design Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.
Contributor(s) Murphy SK, Yang H, Moylan CA, Pang H, Dellinger A, Abdelmalek MF, Garrett ME, Ashley-Koch A, Suzuki A, Tillmann HL, Hauser MA, Diehl AM
Citation(s) 23916847
Submission date Aug 05, 2013
Last update date Mar 22, 2019
Contact name Cynthia Moylan
Organization name Duke University Medical Center
Department Gastroenterology
Street address 595 LaSalle Street, GSRB1, DUMC 3256
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (59)
GSM1201506 NAFLD liver biopsy tissue 15914
GSM1201507 NAFLD liver biopsy tissue 15554
GSM1201508 NAFLD liver biopsy tissue 15445 (replicate 1)
This SubSeries is part of SuperSeries:
GSE31803 Methylome-Transcriptome Relationships in Nonalcoholic Fatty Liver Disease
BioProject PRJNA214554

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE49542_RAW.tar 183.1 Mb (http)(custom) TAR
GSE49542_unmethyl_methyl_signals.txt.gz 127.5 Mb (ftp)(http) TXT
Processed data included within Sample table

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