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ID 52021
FullText URL
Author
Saito, Shunsuke
Kato, Jun
Horii, Joichiro
Suzuki, Hideyuki
Higashi, Reiji
Kaji, Eisuke
Kondo, Yoshitaka ORCID Kaken ID researchmap
Abstract
Background: Although DNA methylation of colonic mucosa in ulcerative colitis (UC) has been suggested, the majority of published reports indicate the correlation between methylation of colon mucosa and occurrence of UC-related dysplasia or cancer without considering the mucosal inflammatory status. The aim of this study was to verify whether mucosal inflammation-specific DNA methylation occurs in the colon of UC. Methods: Of 15 gene loci initially screened, six loci (ABCB1, CDH1. ESR1, GDNF, HPP1, and MYOD1) methylated in colon mucosa of UC were analyzed according to inflammatory status using samples from 28 surgically resected UC patients. Results: Four of six regions (CDH1, GDNF, HPP1, and MYOD1) were more highly methylated in the active inflamed mucosa than in the quiescent mucosa in each UC patient (P = 0.003, 0.0002, 0.02, and 0.048, respectively). In addition, when the methylation status of all samples taken from examined patients was stratified according to inflammatory status, methylation of CDHI and GDNF loci was significantly higher in active inflamed mucosa than in quiescent mucosa (P = 0.045 and 0.002, respectively). Multiple linear regression analysis revealed that active inflammation was an independent factor of methylation for CDHI and GDNF. DNA methyltransferase 1 and 3b were highly expressed in colon epithelial cells with active mucosa] inflammation, suggesting their involvement in inflammation-dependent methylation. Conclusions: Methylation in colonic mucosa of UC was correlated with mucosal inflammatory status, suggesting the involvement of methylation due to chronic active inflammation in UC carcinogenesis.
Keywords
ulcerative colitis
inflammation
methylation
Note
This is a preprint of an article published in http://dx.doi.org/10.1002/ibd.21573
Published Date
2011-09
Publication Title
Inflammatory Bowel Diseases
Volume
volume17
Issue
issue9
Start Page
1955
End Page
1965
ISSN
1078-0998
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1002/ibd.21573
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/51952
language
英語
File Version
author
Refereed
True
DOI
Web of Science KeyUT