DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis
| Autor: | Garret Cullen, Glen A. Doherty, Hugh Mulcahy, Gillian Sexton, Jonathan Mill, Edel McDermott, Elizabeth J. Ryan, Therese M. Murphy, Denise Keegan, R. Alan Harris, Richard Kellermayer, Kevin M. Malone, Joe Burrage, David Gibson, Kathryn R. Byrne, Eimear Crowe, Miriam Tosetto |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent Genome-wide association study Risk Assessment Inflammatory bowel disease Epigenesis Genetic law.invention Pathogenesis Young Adult 03 medical and health sciences Sex Factors Crohn Disease Reference Values law medicine Humans Epigenetics Child Polymerase chain reaction Regulation of gene expression business.industry Gene Expression Profiling Age Factors Gastroenterology General Medicine DNA Methylation Middle Aged Inflammatory Bowel Diseases Prognosis medicine.disease digestive system diseases Gene expression profiling 030104 developmental biology Gene Expression Regulation Case-Control Studies DNA methylation Immunology Disease Progression Colitis Ulcerative Female Original Article business Genome-Wide Association Study |
| Zdroj: | Journal of Crohn's and Colitis. 10:77-86 |
| ISSN: | 1876-4479 1873-9946 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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