title: Downregulation of expression of xenobiotic efflux genes is associated with pelvic pouch inflammation in ulcerative colitis.
abstract: BACKGROUND
  As many as 50% of patients with ulcerative colitis who have undergone ileal pouch-anal anastomosis develop de novo inflammation in the ileal pouch after surgery. With the use of microarray technology, we investigated what gene expression changes occur in the pelvic pouch after surgery for ulcerative colitis and how these changes vary by pouch outcome.
  
  
  METHODS
  Patients who had undergone ileal pouch-anal anastomosis and closure of ileostomy had biopsy specimens from the pouch and pre-pouch ileum prospectively collected. The subjects were allocated into 4 outcome groups: no pouchitis, pouchitis, Crohn's disease-like phenotype, and familial adenomatous polyposis controls. RNA was extracted and transcriptomes were analyzed using a genome-wide approach. The statistical significance of each gene was assessed, and raw P values were corrected for multiple comparisons.
  
  
  RESULTS
  The expression levels of 2733 transcripts in the pouch were significantly associated with outcome. These genes could be classified into 3 categories: regulation of the immune system, modification of the extracellular matrix, and xenobiotic activity. Contrary to the first 2 categories, genes involved in xenobiotic activity, such as ABCB1, had lower expression in the pouchitis and Crohn's disease-like groups compared with the no pouchitis and familial adenomatous polyposis groups.
  
  
  CONCLUSIONS
  Transporters of compounds including xenobiotics are downregulated in recurrent disease after ileal pouch-anal anastomosis, whereas inflammatory pathways are upregulated. These findings corroborate the hypothesis that changes in barrier function could contribute to development of intestinal inflammation.
authors.affiliation: *Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; †Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada; and ‡Division of Gastroenterology, University of Toronto, Toronto, ON, Canada.
authors.forename: Boyko
authors.initials: B
authors.lastname: Kabakchiev
authors.forename: Andrea
authors.initials: A
authors.lastname: Tyler
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Stempak
authors.forename: Raquel
authors.initials: R
authors.lastname: Milgrom
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D039021:Colonic Pouches; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D019449:Pouchitis / Q000235:genetics*; D011446:Prospective Studies; D011519:Proto-Oncogenes / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014157:Transcription Factors