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J Crohns Colitis. 2016 Jan;10(1):77-86. doi: 10.1093/ecco-jcc/jjv176. Epub 2015 Sep 28.

DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis.

Author information

1
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
2
Centre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
3
University of Exeter Medical School, University of Exeter, Exeter, Devon, UK.
4
School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland Department of Psychiatry, Psychotherapy & Mental Health Research, St Vincent's University Hospital, Dublin, Ireland.
5
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
6
Department of Pediatrics, Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Texas Children's Hospital, Houston, TX, USA.
7
University of Exeter Medical School, University of Exeter, Exeter, Devon, UK MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Abstract

BACKGROUND AND AIMS:

Inflammatory bowel diseases (IBDs) are heterogeneous disorders with complex aetiology. Quantitative genetic studies suggest that only a small proportion of the disease variance observed in IBD is accounted for by genetic variation, indicating a potential role for differential epigenetic regulation in disease aetiology. The aim of this study was to assess genome-wide DNA methylation changes specifically associated with ulcerative colitis (UC), Crohn's disease (CD) and IBD activity.

METHODS:

DNA methylation was quantified in peripheral blood mononuclear cells (PBMCs) from 149 IBD cases (61 UC, 88 CD) and 39 controls using the Infinium HumanMethylation450 BeadChip. Technical and functional validation was performed using pyrosequencing and the real-time polymerase chain reaction. Cross-tissue replication of the top differentially methylated positions (DMPs) was tested in colonic mucosa tissue samples obtained from paediatric IBD cases and controls.

RESULTS:

A total of 3196 probes were differentially methylated between CD cases and controls, while 1481 probes were differentially methylated between UC cases and controls. There was considerable (45%) overlap between UC and CD DMPs. The top-ranked IBD-associated PBMC differentially methylated region (promoter region of TRIM39-RPP2) was also significantly hypomethylated in colonic mucosa from paediatric UC patients. In addition, we confirmed TRAF6 hypermethylation using pyrosequencing and found reduced TRAF6 gene expression in PBMCs of IBD patients.

CONCLUSIONS:

Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.

KEYWORDS:

DNA methylation; Epigenetics; inflammatory bowel disease

PMID:
26419460
PMCID:
PMC5013897
DOI:
10.1093/ecco-jcc/jjv176
[Indexed for MEDLINE]
Free PMC Article

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