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Regional variation in gene expression in the healthy colon is dysregulated in ulcerative colitis.
- Source :
- Gut; Oct2008, Vol. 57 Issue 10, p1398-1405, 8p, 3 Diagrams, 5 Charts, 3 Graphs
- Publication Year :
- 2008
-
Abstract
- Objective: To investigate differential intestinal gene expression in patients with ulcerative colitis and in controls. Design: Genome-wide expression study (41 058 expression sequence tags, 215 biopsies). Setting: Western General Hospital, Edinburgh, UK, and Genentech, San Francisco, USA. Patients: 67 patients with ulcerative colitis and 31 control subjects (23 normal subjects and 8 patients with inflamed non-inflammatory bowel disease biopsies). Interventions: Paired endoscopic biopsies were taken from 5 specific anatomical locations for ANA extraction and histology. The Agilent microarray platform was used and confirmation of results was undertaken by real time polymerase chain reaction and immunohistochemistry. Results: In healthy control biopsies, cluster analysis showed differences in gene expression between the right and left colon. (χ<superscript>2</superscript> = 25.1, p<0.0001). Developmental genes, homeobox protein A13 (HOXA13), (p = 2.3×10<superscript>-16</superscript>), HOXB13 (p<1 × 10<superscript>-45</superscript>), glioma-associated oncogene 1 (GLI1) (p = 4.0 × 10<superscript>-24</superscript>), and GLI3 (p = 2.1 × 10<superscript>-28</superscript>) primarily drove this separation. When all ulcerative colitis biopsies and control biopsies were compared, 143 sequences had a fold change of >1.5 in the ulcerative colitis biopsies (0.01 >p>10<superscript>-45</superscript>) and 54 sequences had a fold change of <-1.5 (0.01 >p>10<superscript>-20</superscript>). Differentially upregulated genes in ulcerative colitis included serum amyloid A1 (SAA1) (p<10<superscript>-45</superscript>) the alpha defensins 5 and 6 (DEFA5 and 6) (p = 0.00003 and p = 6.95 × 10<superscript>-7</superscript>, respectively), matrix metalloproteinase 3 (MMP3) (p = 5.6 × 10<superscript>-10</superscript>) and MMP7 (p = 2.3 × 10<superscript>-7</superscript>). Increased DEFA5 and 6 expression was further characterised to Paneth cell metaplasia by immunohistochemistry and in situ hybridisation. Sub-analysis of the inflammatory bowel disease 2 (IBD2) and IBD5 loci, and the ATP-binding cassette (ABC) transporter genes revealed a number of differentially regulated genes in the ulcerative colitis biopsies. Conclusions: Key findings are the expression gradient in the healthy adult colon and the involvement of novel gene families, as well as established candidate genes in the pathogenesis of ulcerative colitis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00175749
- Volume :
- 57
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Gut
- Publication Type :
- Academic Journal
- Accession number :
- 34640822
- Full Text :
- https://doi.org/10.1136/gut.2008.148395