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DNA methylation-associated colonic mucosal immune and defense responses in treatment-naïve pediatric ulcerative colitis
RA. Harris, D. Nagy-Szakal, SA. Mir, E. Frank, R. Szigeti, JL. Kaplan, J. Bronsky, A. Opekun, GD. Ferry, H. Winter, R. Kellermayer,
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2006 to 1 year ago
PubMed Central
from 2010
Europe PubMed Central
from 2010 to 1 year ago
PubMed
24937444
DOI
10.4161/epi.29446
Knihovny.cz E-resources
- MeSH
- Crohn Disease genetics immunology MeSH
- Child MeSH
- Epigenesis, Genetic MeSH
- Gene Expression MeSH
- Colon immunology MeSH
- Humans MeSH
- DNA Methylation immunology MeSH
- Adolescent MeSH
- Young Adult MeSH
- Child, Preschool MeSH
- Immunity, Mucosal MeSH
- Intestinal Mucosa immunology MeSH
- Case-Control Studies MeSH
- Colitis, Ulcerative genetics immunology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn's disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P<0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.
Charles University and University Hospital Motol
Department of Computer Science
Department of Gastroenterology
Department of Molecular and Human Genetics
References provided by Crossref.org
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- $a Inflammatory bowel diseases (IBD) are emerging globally, indicating that environmental factors may be important in their pathogenesis. Colonic mucosal epigenetic changes, such as DNA methylation, can occur in response to the environment and have been implicated in IBD pathology. However, mucosal DNA methylation has not been examined in treatment-naïve patients. We studied DNA methylation in untreated, left sided colonic biopsy specimens using the Infinium HumanMethylation450 BeadChip array. We analyzed 22 control (C) patients, 15 untreated Crohn's disease (CD) patients, and 9 untreated ulcerative colitis (UC) patients from two cohorts. Samples obtained at the time of clinical remission from two of the treatment-naïve UC patients were also included into the analysis. UC-specific gene expression was interrogated in a subset of adjacent samples (5 C and 5 UC) using the Affymetrix GeneChip PrimeView Human Gene Expression Arrays. Only treatment-naïve UC separated from control. One-hundred-and-twenty genes with significant expression change in UC (> 2-fold, P<0.05) were associated with differentially methylated regions (DMRs). Epigenetically associated gene expression changes (including gene expression changes in the IFITM1, ITGB2, S100A9, SLPI, SAA1, and STAT3 genes) were linked to colonic mucosal immune and defense responses. These findings underscore the relationship between epigenetic changes and inflammation in pediatric treatment-naïve UC and may have potential etiologic, diagnostic, and therapeutic relevance for IBD.
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