PMID- 18523026
OWN - NLM
STAT- MEDLINE
DCOM- 20081016
LR  - 20220316
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Linking)
VI  - 57
IP  - 10
DP  - 2008 Oct
TI  - Regional variation in gene expression in the healthy colon is dysregulated in 
      ulcerative colitis.
PG  - 1398-405
LID - 10.1136/gut.2008.148395 [doi]
AB  - 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 
      RNA 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. (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. 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.
FAU - Noble, C L
AU  - Noble CL
AD  - Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, 
      Edinburgh, EH4 2XU, UK. noblecolin@hotmail.com
FAU - Abbas, A R
AU  - Abbas AR
FAU - Cornelius, J
AU  - Cornelius J
FAU - Lees, C W
AU  - Lees CW
FAU - Ho, G-T
AU  - Ho GT
FAU - Toy, K
AU  - Toy K
FAU - Modrusan, Z
AU  - Modrusan Z
FAU - Pal, N
AU  - Pal N
FAU - Zhong, F
AU  - Zhong F
FAU - Chalasani, S
AU  - Chalasani S
FAU - Clark, H
AU  - Clark H
FAU - Arnott, I D
AU  - Arnott ID
FAU - Penman, I D
AU  - Penman ID
FAU - Satsangi, J
AU  - Satsangi J
FAU - Diehl, L
AU  - Diehl L
LA  - eng
GR  - G0701898/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
DEP - 20080603
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Colitis, Ulcerative/*genetics
MH  - Colon/*metabolism
MH  - Disease Susceptibility/metabolism
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Genome, Human/genetics
MH  - Germ-Line Mutation/genetics
MH  - Humans
MH  - Ileum/metabolism
MH  - Male
MH  - Polymerase Chain Reaction
MH  - RNA/metabolism
MH  - Up-Regulation
EDAT- 2008/06/05 09:00
MHDA- 2008/10/17 09:00
CRDT- 2008/06/05 09:00
PHST- 2008/06/05 09:00 [pubmed]
PHST- 2008/10/17 09:00 [medline]
PHST- 2008/06/05 09:00 [entrez]
AID - gut.2008.148395 [pii]
AID - 10.1136/gut.2008.148395 [doi]
PST - ppublish
SO  - Gut. 2008 Oct;57(10):1398-405. doi: 10.1136/gut.2008.148395. Epub 2008 Jun 3.