Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review.
As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people i...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024106&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849419204298539008 |
|---|---|
| author | Isabelle Cleynen Peter Jüni Geertruida E Bekkering Eveline Nüesch Camila T Mendes Stefanie Schmied Stefan Wyder Eliane Kellen Peter M Villiger Paul Rutgeerts Séverine Vermeire Daniel Lottaz |
| author_facet | Isabelle Cleynen Peter Jüni Geertruida E Bekkering Eveline Nüesch Camila T Mendes Stefanie Schmied Stefan Wyder Eliane Kellen Peter M Villiger Paul Rutgeerts Séverine Vermeire Daniel Lottaz |
| author_sort | Isabelle Cleynen |
| collection | DOAJ |
| description | As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4 protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family. |
| format | Article |
| id | doaj-art-e749fd9344b6407cbf05b9523528828c |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e749fd9344b6407cbf05b9523528828c2025-08-20T03:32:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2410610.1371/journal.pone.0024106Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review.Isabelle CleynenPeter JüniGeertruida E BekkeringEveline NüeschCamila T MendesStefanie SchmiedStefan WyderEliane KellenPeter M VilligerPaul RutgeertsSéverine VermeireDaniel LottazAs part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4 protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024106&type=printable |
| spellingShingle | Isabelle Cleynen Peter Jüni Geertruida E Bekkering Eveline Nüesch Camila T Mendes Stefanie Schmied Stefan Wyder Eliane Kellen Peter M Villiger Paul Rutgeerts Séverine Vermeire Daniel Lottaz Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. PLoS ONE |
| title | Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. |
| title_full | Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. |
| title_fullStr | Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. |
| title_full_unstemmed | Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. |
| title_short | Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review. |
| title_sort | genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease a systematic review |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0024106&type=printable |
| work_keys_str_mv | AT isabellecleynen geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT peterjuni geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT geertruidaebekkering geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT evelinenuesch geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT camilatmendes geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT stefanieschmied geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT stefanwyder geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT elianekellen geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT petermvilliger geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT paulrutgeerts geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT severinevermeire geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview AT daniellottaz geneticevidencesupportingtheassociationofproteaseandproteaseinhibitorgeneswithinflammatoryboweldiseaseasystematicreview |