DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with ulcerative colitis (UC).
BACKGROUND
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 no studies exist that assess its relationship with lifestyle exposures.


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.


OBJECTIVE
To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor-1) and N-33 (tumor 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) while gene specific methylation was quantified using the COBRA method.


CONCLUSIONS
For the first time, we have shown increased methylation in the promoter regions of the putative tumor 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 suggest that inactivation through methylation of the putative tumor suppressor genes N-33 and ESR-1 may not be associated with colorectal carcinogenesis in UC.
Arasaradnam
Ramesh P
RP
Human Nutrition Research Centre, Newcastle University, Newcastle, UK. r.arasaradnam@warwick.ac.uk
Khoo
Kevin
K
Bradburn
Mike
M
Mathers
John C
JC
Kelly
Seamus B
SB
D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012007:Rectum / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins