Article Text

other Versions

PDF
Regional Variation in Gene Expression in the Healthy Colon is Dysregulated in Ulcerative Colitis
  1. Colin L Noble (noblecolin{at}hotmail.com)
  1. University of Edinburgh, United Kingdom
    1. Alexander R Abbas (abbas{at}gene.com)
    1. Genentech Inc, United States
      1. Jennine Cornelius (jennine813{at}gmail.com)
      1. Genentech Inc, United States
        1. Charlie W Lees (charlie.lees{at}ed.ac.uk)
        1. University of Edinburgh, United Kingdom
          1. Gwo- Tzer Ho (gwotzerho{at}aol.co.uk)
          1. University of Edinburgh, United Kingdom
            1. Karen Toy (toy.karen{at}gene.com)
            1. Genentech Inc, United States
              1. Zora Modrusan (z.modrusan{at}gene.com)
              1. Genentech Inc, United States
                1. Navneet Pal (n.pal{at}gene.com)
                1. Genentech Inc, United States
                  1. Fiona Zhong (f.zhong{at}gene.com)
                  1. Genentech Inc, United States
                    1. Sreedevi Chalasani (s.chalasani{at}gene.com)
                    1. Genentech Inc, United States
                      1. Hilary Clark (h.clark{at}gene.com)
                      1. Genentech Inc, United States
                        1. Ian D Arnott (ian.arnott{at}luht.scot.nhs.uk)
                        1. University of Edinburgh, United Kingdom
                          1. Ian D Penman (ian.penman{at}luht.scot.nhs.uk)
                          1. University of Edinburgh, United Kingdom
                            1. Jack Satsangi (j.satsangi{at}ed.ac.uk)
                            1. University of Edinburgh, United Kingdom
                              1. Lauri Diehl (ldiehl{at}gene.com)
                              1. Genentech Inc, United States

                                Abstract

                                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<0.0001). Developmental genes HOXA13, (p=2.3x10-16), HOXB13 (p <1x10-45), GLI1 (p=4.0x10-24), and GLI3 (p=2.1x10-28) primarily drove this separation. When all UC biopsies and control biopsies were compared, 143 sequences had a fold change of >1.5 in the UC 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 UC included SAA1 (p<10-45) the alpha defensins, DEFA5&6 (p=0.00003 and p=6.95x10-7 respectively), MMP3 (p=5.6x10-10) and MMP7 (p=2.3x10-7). Increased DEFA5&6 expression was further characterized to Paneth cell metaplasia by immunohistochemistry and in-situ hybridization. Sub-analysis of the IBD2 & IBD5 loci, and the ABC transporter genes revealed a number of differentially regulated genes in the UC 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 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.