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Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease

Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while in...

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Autores principales: Morsy, Yasser, Brillant, Nathalie, Franc, Yannick, Scharl, Michael, Wawrzyniak, Marcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700574/
https://www.ncbi.nlm.nih.gov/pubmed/34944097
http://dx.doi.org/10.3390/cells10123589
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author Morsy, Yasser
Brillant, Nathalie
Franc, Yannick
Scharl, Michael
Wawrzyniak, Marcin
author_facet Morsy, Yasser
Brillant, Nathalie
Franc, Yannick
Scharl, Michael
Wawrzyniak, Marcin
author_sort Morsy, Yasser
collection PubMed
description Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.
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spelling pubmed-87005742021-12-24 Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease Morsy, Yasser Brillant, Nathalie Franc, Yannick Scharl, Michael Wawrzyniak, Marcin Cells Article Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD. MDPI 2021-12-20 /pmc/articles/PMC8700574/ /pubmed/34944097 http://dx.doi.org/10.3390/cells10123589 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morsy, Yasser
Brillant, Nathalie
Franc, Yannick
Scharl, Michael
Wawrzyniak, Marcin
Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease
title Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease
title_full Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease
title_fullStr Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease
title_full_unstemmed Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease
title_short Unravelling the Impact of the Genetic Variant rs1042058 within the TPL2 Risk Gene Locus on Molecular and Clinical Disease Course Patients with Inflammatory Bowel Disease
title_sort unravelling the impact of the genetic variant rs1042058 within the tpl2 risk gene locus on molecular and clinical disease course patients with inflammatory bowel disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700574/
https://www.ncbi.nlm.nih.gov/pubmed/34944097
http://dx.doi.org/10.3390/cells10123589
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