Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA methylation analysis in non-alcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients with all stages of NAFLD and controls were analysed by array-based DNA methylation and mRNA expression profiling. Bisulphite converted DNA from the 85 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

ORGANISM(S): Homo sapiens

SUBMITTER: Ole Ammerpohl

PROVIDER: E-GEOD-48325 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.

Ahrens Markus M Ammerpohl Ole O von Schönfels Witigo W Kolarova Julia J Bens Susanne S Itzel Timo T Teufel Andreas A Herrmann Alexander A Brosch Mario M Hinrichsen Holger H Erhart Wiebke W Egberts Jan J Sipos Bence B Schreiber Stefan S Häsler Robert R Stickel Felix F Becker Thomas T Krawczak Michael M Röcken Christoph C Siebert Reiner R Schafmayer Clemens C Hampe Jochen J

Cell metabolism 20130801 2

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (n = 45) with all stages of NAFLD and controls (n = 18) were analyzed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, and PLCG1) and insulin/insulin-like signaling (including IGF1, ...[more]

PMID: 23931760

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Project description: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. 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.

Dataset Information

DNA methylation analysis in non-alcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery

Publications

DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.

Similar Datasets

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