+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Regional variation in gene expression in the healthy colon is dysregulated in ulcerative colitis

Gut 57(10): 1398-1405
Regional variation in gene expression in the healthy colon is dysregulated in ulcerative colitis
To investigate differential intestinal gene expression in patients with ulcerative colitis and in controls. Genome-wide expression study (41,058 expression sequence tags, 215 biopsies). Western General Hospital, Edinburgh, UK, and Genentech, San Francisco, USA. 67 patients with ulcerative colitis and 31 control subjects (23 normal subjects and 8 patients with inflamed non-inflammatory bowel disease biopsies). Paired endoscopic biopsies were taken from 5 specific anatomical locations for RNA extraction and histology. The Agilent microarray platform was used and confirmation of results was undertaken by real time polymerase chain reaction and immunohistochemistry. In healthy control biopsies, cluster analysis showed differences in gene expression between the right and left colon. (chi(2) = 25.1, p<0.0001). Developmental genes, homeobox protein A13 (HOXA13), (p = 2.3x10(-16)), HOXB13 (p<1x10(-45)), glioma-associated oncogene 1 (GLI1) (p = 4.0x10(-24)), and GLI3 (p = 2.1x10(-28)) 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(-45)) and 54 sequences had a fold change of <-1.5 (0.01>p>10(-20)). Differentially upregulated genes in ulcerative colitis included serum amyloid A1 (SAA1) (p<10(-45)) the alpha defensins 5 and 6 (DEFA5 and 6) (p = 0.00003 and p = 6.95x10(-7), respectively), matrix metalloproteinase 3 (MMP3) (p = 5.6x10(-10)) and MMP7 (p = 2.3x10(-7)). 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. 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.

(PDF same-day service: $19.90)

Accession: 055445089

PMID: 18523026

DOI: 10.1136/gut.2008.148395

Related references

Illness experience and life stresses in patients with irritable colon and with ulcerative colitis. An epidemiologic study of ulcerative colitis and regional enteritis in Baltimore, 1960-1964. New England Journal of Medicine 282(1): 14-17, 1970

Interferon-inducible gene family 1-8U expression in colitis-associated colon cancer and severely inflamed mucosa in ulcerative colitis. Cancer Research 59(23): 5927-5931, 1999

Gene expression of VIP in sigmoid colon from chronic ulcerative colitis. Gastroenterology 104(4 SUPPL ): A578, 1993

Ulcerative colitis serum immuno globulin g recognizes an antigen in a human colon cancer cell line and in ulcerative colitis colon. Gastroenterology 78(5 PART 2): 1227, 1980

Dysregulated Tim-3 expression and its correlation with imbalanced CD4 helper T cell function in ulcerative colitis. Clinical Immunology 145(3): 230-240, 2013

Differentiation of ulcerative colitis and regional enteritis of colon. Archives of Pathology 89(1): 20-29, 1970

Increased expression of discs large homolog 5 gene (DLG5) in ulcerative colitis patients compared to healthy individuals. Inflammatory Bowel Diseases 17(7): 1639-1639, 2011

Regional proliferative patterns in the colon of patients with ulcerative colitis and controls. Gastroenterology 106(4 SUPPL ): A426, 1994

Regional enteritis of the colon: a clinical and pathologic comparison with ulcerative colitis. American Journal of Digestive Diseases 13(6): 501-514, 1968

Metachronous development of regional enteritis of the colon in a patient with ulcerative colitis. California Medicine 114(3): 80-84, 1971