Regional Variation in Gene Expression in the Healthy Colon is Dysregulated in Ulcerative Colitis

Objective: The aim of this study was to investigate differential intestinal gene expression in patients with ulcerative colitis (UC) and controls. Design: Genome wide expression study (41058 expression sequence tags, 215 biopsies). Setting: Western General Hospital, Edinburgh, UK, Genentech Inc, San Francisco, USA. Patients: 67 UC and 31 control subjects- 23 normal and 8 inflamed non-inflammatory bowel disease patients. Interventions: 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 PCR and immunohistochemistry. Results: In healthy control biopsies, cluster analysis showed differences in gene expression between the right and left colon. (χ2=25.1, p 1.5 in the UC biopsies (0.01>p>10-45) and 54 sequences had a fold change of p>10-20). Differentially upregulated genes in UC included SAA1 (p 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 UC.