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Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis

Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis


Title: Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis
Author: Vinayaga-Pavan, Mathena
Frampton, Matthew
Pontikos, Nikolas
Levine, Adam P
Smith, Phillip J
Jonasson, Jon G.
Bjornsson, Einar   orcid.org/0000-0002-8392-0632
Segal, Anthony W
Smith, Andrew M
Date: 2018-11-19
Language: English
Scope: 317-327
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Department: Læknadeild (HÍ)
Faculty of Medicine (UI)
Series: Inflammatory Bowel Diseases;25(2)
ISSN: 1078-0998
1536-4844 (eISSN)
DOI: 10.1093/ibd/izy350
Subject: Gastroenterology; Inflammatory bowel disease; Microarray; Rectum; TPMT; Meltingarfærasjúkdómar; Bólgur; Endaþarmur
URI: https://hdl.handle.net/20.500.11815/1857

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Citation:

Mathena Vinayaga-Pavan, MRCP, Matthew Frampton, PhD, Nikolas Pontikos, PhD, Adam P Levine, MBBS PhD, Phillip J Smith, MRCP, Jon G Jonasson, MD, Einar S Björnsson, MD PhD, Anthony W Segal, MD PhD, Andrew M Smith, PhD, Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis, Inflammatory Bowel Diseases, Volume 25, Issue 2, February 2019, Pages 317–327, https://doi.org/10.1093/ibd/izy350

Abstract:

Background: A combination of genetic and environmental factors is thought to be involved in the pathogenesis of ulcerative colitis (UC). In Iceland, the incidence of UC is one of the highest in the world. The aim of this study was to characterize patients with UC and identify potential germline mutations and pathways that could be associated with UC in this population. Methods: Exome sequencing and genome-wide microarray analysis on macroscopically noninflamed colonic mucosa from patients and controls were performed. Exome sequence data were examined for very rare or novel mutations that were over-represented in the UC cohort. Combined matching of variant analysis and downstream influence on transcriptomic expression in the rectum were analyzed. Results: One thousand eight hundred thirty-eight genes were differentially expressed in rectal tissue from UC patients and identified an upregulation in genes associated with cell cycle control and protein processing in the endoplasmic reticulum (ER). Two missense mutations in thiopurine S-methyltransferase (TPMT) with a minor allele frequency of 0.22 in the UC patients compared with a reported 0.062 in the Icelandic population were identified. A predicted damaging mutation in the gene SLC26A3 is potentially associated with increased expression of DUOX2 and DUOXA2 in rectal tissue. Conclusions: Colonic mucosa of UC patients demonstrates evidence of an elevation in genes involving cell proliferation and processing of proteins within the ER. Exome sequencing identified a possible increased prevalence of 2 damaging TPMT variants within the UC population, suggesting screening the UC population before initiation of thiopurine analogue therapy to avoid toxicity associated with these mutations.

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited

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