Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis
Publisher's version (útgefin grein) 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 wit...
Published in: | Inflammatory Bowel Diseases |
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Language: | English |
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Oxford University Press (OUP)
2018
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Online Access: | https://hdl.handle.net/20.500.11815/1857 https://doi.org/10.1093/ibd/izy350 |
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ftopinvisindi:oai:opinvisindi.is:20.500.11815/1857 2023-05-15T16:52:07+02:00 Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis Vinayaga-Pavan, Mathena Frampton, Matthew Pontikos, Nikolas Levine, Adam P Smith, Phillip J Jonasson, Jon G. Bjornsson, Einar Segal, Anthony W Smith, Andrew M Læknadeild (HÍ) Faculty of Medicine (UI) Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Háskóli Íslands University of Iceland 2018-11-19 317-327 https://hdl.handle.net/20.500.11815/1857 https://doi.org/10.1093/ibd/izy350 en eng Oxford University Press (OUP) Inflammatory Bowel Diseases;25(2) http://academic.oup.com/ibdjournal/article-pdf/25/2/317/27470908/izy350.pdf 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 1078-0998 1536-4844 (eISSN) https://hdl.handle.net/20.500.11815/1857 Inflammatory Bowel Diseases doi:10.1093/ibd/izy350 info:eu-repo/semantics/openAccess Gastroenterology Inflammatory bowel disease Microarray Rectum TPMT Meltingarfærasjúkdómar Bólgur Endaþarmur info:eu-repo/semantics/article 2018 ftopinvisindi https://doi.org/20.500.11815/1857 https://doi.org/10.1093/ibd/izy350 2022-11-18T06:51:57Z Publisher's version (útgefin grein) 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. UCL genomics for technical assistance with microarray. Patients and control subjects who kindly donated samples for this study. Peer Reviewed Article in Journal/Newspaper Iceland Opin vísindi (Iceland) Inflammatory Bowel Diseases 25 2 317 327 |
institution |
Open Polar |
collection |
Opin vísindi (Iceland) |
op_collection_id |
ftopinvisindi |
language |
English |
topic |
Gastroenterology Inflammatory bowel disease Microarray Rectum TPMT Meltingarfærasjúkdómar Bólgur Endaþarmur |
spellingShingle |
Gastroenterology Inflammatory bowel disease Microarray Rectum TPMT Meltingarfærasjúkdómar Bólgur Endaþarmur Vinayaga-Pavan, Mathena Frampton, Matthew Pontikos, Nikolas Levine, Adam P Smith, Phillip J Jonasson, Jon G. Bjornsson, Einar Segal, Anthony W Smith, Andrew M Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis |
topic_facet |
Gastroenterology Inflammatory bowel disease Microarray Rectum TPMT Meltingarfærasjúkdómar Bólgur Endaþarmur |
description |
Publisher's version (útgefin grein) 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. UCL genomics for technical assistance with microarray. Patients and control subjects who kindly donated samples for this study. Peer Reviewed |
author2 |
Læknadeild (HÍ) Faculty of Medicine (UI) Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Háskóli Íslands University of Iceland |
format |
Article in Journal/Newspaper |
author |
Vinayaga-Pavan, Mathena Frampton, Matthew Pontikos, Nikolas Levine, Adam P Smith, Phillip J Jonasson, Jon G. Bjornsson, Einar Segal, Anthony W Smith, Andrew M |
author_facet |
Vinayaga-Pavan, Mathena Frampton, Matthew Pontikos, Nikolas Levine, Adam P Smith, Phillip J Jonasson, Jon G. Bjornsson, Einar Segal, Anthony W Smith, Andrew M |
author_sort |
Vinayaga-Pavan, Mathena |
title |
Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis |
title_short |
Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis |
title_full |
Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis |
title_fullStr |
Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis |
title_full_unstemmed |
Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis |
title_sort |
elevation in cell cycle and protein metabolism gene transcription in inactive colonic tissue from icelandic patients with ulcerative colitis |
publisher |
Oxford University Press (OUP) |
publishDate |
2018 |
url |
https://hdl.handle.net/20.500.11815/1857 https://doi.org/10.1093/ibd/izy350 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
Inflammatory Bowel Diseases;25(2) http://academic.oup.com/ibdjournal/article-pdf/25/2/317/27470908/izy350.pdf 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 1078-0998 1536-4844 (eISSN) https://hdl.handle.net/20.500.11815/1857 Inflammatory Bowel Diseases doi:10.1093/ibd/izy350 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/20.500.11815/1857 https://doi.org/10.1093/ibd/izy350 |
container_title |
Inflammatory Bowel Diseases |
container_volume |
25 |
container_issue |
2 |
container_start_page |
317 |
op_container_end_page |
327 |
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1766042257534746624 |