Article Text

PDF
OC-047 Colonic expression profiles of genes identified by genome wide association scan in ulcerative colitis
  1. C L Noble1,
  2. A R Abbas2,
  3. C W Lees1,
  4. L Diehl3,
  5. J Satsangi1
  1. 1Gastrointestinal Unit, University of Edinburgh, Edinburgh, UK
  2. 2Department of Bioinformatics, Genentech, San Francisco, California, USA
  3. 3Department of Pathology, Genentech, San Francisco, California, USA

Abstract

Introduction Genome wide expression analysis using microarray allows a comprehensive picture of gene expression at the tissue and cellular level. The aim of this study was to investigate the differential expression of 26 genes recently identified by Barrett et al as being associated with ulcerative colitis (UC).1

Methods 67 Ulcerative colitis patients (UC) and 31 controls (HC) were studied. 129 UC and 73 HC paired endoscopic biopsies were taken from specific anatomical locations for RNA extraction and histology assessment. Expression signatures were investigated using 39 probes representing the 26 genes using the Agilent microarray platform.

Results When all the UC biopsies were compared to controls MST1 was the most dysregulated gene- fold change (FC) −1.64, p <0.00001 in the UC biopsies. HERC2 was also downregulated in the UC biopsies (FC −1.2, p <0.00001) as was CCNY (FC −1.2, p=0.0001). TNFRSF6B was significantly upregulated (FC +1.2, p=0.005). When inflamed and non-inflamed descending and sigmoid colon UC biopsies were compared TNFRSF6B was upregulated (FC +2.98, p <0.00001) as was MHC (FC +1.88, p=0.027), the novel susceptibility genes LAMB1 (FC +1.23, p=0.0058), HNF4A (FC +1.23, p=0.024) and ARPC2 (FC +1.20, p=0.01). MST1 (FC −1.76, p=0.015) and CCNY (FC −1.42, p=0.001) were downregulated in the inflamed UC biopsies. HERC2 was the only significantly dysregulated gene when non-inflamed UC and control biopsies were compared (FC −1.20, p=0.0028) and was downregulated in UC.

Conclusion Disease and inflammation dependent expression changes were observed in a number of the UC genome wide expression scan susceptibility genes further implicating them in the pathogenesis of UC.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.