Type

Journal Article

Authors

Therese M Murphy
Hugh Mulcahy
Glen A Doherty
Garret Cullen
Jonathan Mill
Richard Kellermayer
R Alan Harris
Kevin Malone
Gillian Sexton
Eimear Crowe
and 7 others

Subjects

Veterinary

Topics
dna profiling gene expression real time polymerase chain reaction genetic variation inflammatory bowel diseases dna methylation blood cells inflammatory bowel disease

DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis. (2015)

Abstract 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. 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. 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. Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Therese M Murphy, Hugh Mulcahy, Glen A Doherty, Garret Cullen, Jonathan Mill, Richard Kellermayer, R Alan Harris, Kevin Malone, Gillian Sexton, Eimear Crowe and 7 others

Experts in our system

1
Hugh E Mulcahy
University College Dublin
Total Publications: 43
 
2
Glen A Doherty
University College Dublin
Total Publications: 57
 
3
Garret Cullen
University College Dublin
Total Publications: 17
 
4
Kevin M Malone
University College Dublin
Total Publications: 27