DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)
Arasaradnam, Ramesh P., Khoo, K. T. J., Bradburn, Mike, Mathers, John C. and Kelly, S. B.. (2010) DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC). Epigenetics, Vol.5 (No.5). pp. 422-426. ISSN 1559-2294
WRAP_Arasaradnam_Revised_Manuscript_Epigenetics_2010EPI0026_(3).pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://www.landesbioscience.com/journals/7/article...
Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures.
Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method.
Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected.
Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC.
|Item Type:||Journal Article|
|Alternative Title:||DNA methylation of ESR-1 and N-33 in Ulcerative Colitis|
|Subjects:||Q Science > QP Physiology
R Medicine > RC Internal medicine
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Library of Congress Subject Headings (LCSH):||DNA -- Methylation, Antioncogenes, Ulcerative colitis, Gastrointestinal mucosa|
|Journal or Publication Title:||Epigenetics|
|Official Date:||1 July 2010|
|Page Range:||pp. 422-426|
|Access rights to Published version:||Open Access|
|Funder:||Great Britain. Food Standards Agency (FSA), Ileostomy Association of Great Britain and Ireland|
|Grant number:||N12105 (FSA)|
1. Bird AP. The relationship of DNA methylation to cancer. Cancer Surv 1996;28: 87-101.
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