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.

Details

Ressource 1Download: 34944097_BIB_B1001811F13B.pdf (4112.34 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B1001811F13B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
Cells
Author(s)
Morsy Y., Brillant N., Franc Y., Scharl M., Wawrzyniak M.
Working group(s)
On Behalf Of The Swiss Ibd Cohort Study Group
ISSN
2073-4409 (Electronic)
ISSN-L
2073-4409
Publication state
Published
Issued date
20/12/2021
Peer-reviewed
Oui
Volume
10
Number
12
Pages
3589
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Adolescent, Adult, Alleles, Arthritis/blood, Arthritis/genetics, Colitis, Ulcerative/blood, Colitis, Ulcerative/genetics, Colitis, Ulcerative/surgery, Crohn Disease/blood, Crohn Disease/genetics, Cytokines/blood, Cytokines/genetics, Cytokines/metabolism, Disease Progression, Factor Analysis, Statistical, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Inflammatory Bowel Diseases/genetics, Inflammatory Bowel Diseases/pathology, MAP Kinase Kinase Kinases/genetics, Male, Polymorphism, Single Nucleotide/genetics, Proto-Oncogene Proteins/genetics, RNA, Messenger/genetics, RNA, Messenger/metabolism, Risk Factors, Young Adult, Crohn’s disease, IBD, TPL2, ulcerative colitis
Pubmed
Web of science
Open Access
Yes
Create date
28/12/2021 17:03
Last modification date
08/08/2024 7:38
Usage data