The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease.
Inflammatory bowel disease
genetics
proteomics
Journal
Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676
Informations de publication
Date de publication:
14 Mar 2022
14 Mar 2022
Historique:
pubmed:
8
9
2021
medline:
17
3
2022
entrez:
7
9
2021
Statut:
ppublish
Résumé
Protein profiling in patients with inflammatory bowel diseases [IBD] for diagnostic and therapeutic purposes is underexplored. This study analysed the association between phenotype, genotype, and the plasma proteome in IBD. A total of 92 inflammation-related proteins were quantified in plasma of 1028 patients with IBD (567 Crohn's disease [CD]; 461 ulcerative colitis [UC]) and 148 healthy individuals to assess protein-phenotype associations. Corresponding whole-exome sequencing and global screening array data of 919 patients with IBD were included to analyse the effect of genetics on protein levels (protein quantitative trait loci [pQTL] analysis). Intestinal mucosal RNA sequencing and faecal metagenomic data were used for complementary analyses. Thirty-two proteins were differentially abundant between IBD and healthy individuals, of which 22 proteins were independent of active inflammation; 69 proteins were associated with 15 demographic and clinical factors. Fibroblast growth factor-19 levels were decreased in CD patients with ileal disease or a history of ileocecal resection. Thirteen novel cis-pQTLs were identified and 10 replicated from previous studies. One trans-pQTL of the fucosyltransferase 2 [FUT2] gene [rs602662] and two independent cis-pQTLs of C-C motif chemokine 25 [CCL25] affected plasma CCL25 levels. Intestinal gene expression data revealed an overlapping cis-expression [e]QTL-variant [rs3745387] of the CCL25 gene. The FUT2 rs602662 trans-pQTL was associated with reduced abundances of faecal butyrate-producing bacteria. This study shows that genotype and multiple disease phenotypes strongly associate with the plasma inflammatory proteome in IBD, and identifies disease-associated pathways that may help to improve disease management in the future.
Sections du résumé
BACKGROUND AND AIMS
OBJECTIVE
Protein profiling in patients with inflammatory bowel diseases [IBD] for diagnostic and therapeutic purposes is underexplored. This study analysed the association between phenotype, genotype, and the plasma proteome in IBD.
METHODS
METHODS
A total of 92 inflammation-related proteins were quantified in plasma of 1028 patients with IBD (567 Crohn's disease [CD]; 461 ulcerative colitis [UC]) and 148 healthy individuals to assess protein-phenotype associations. Corresponding whole-exome sequencing and global screening array data of 919 patients with IBD were included to analyse the effect of genetics on protein levels (protein quantitative trait loci [pQTL] analysis). Intestinal mucosal RNA sequencing and faecal metagenomic data were used for complementary analyses.
RESULTS
RESULTS
Thirty-two proteins were differentially abundant between IBD and healthy individuals, of which 22 proteins were independent of active inflammation; 69 proteins were associated with 15 demographic and clinical factors. Fibroblast growth factor-19 levels were decreased in CD patients with ileal disease or a history of ileocecal resection. Thirteen novel cis-pQTLs were identified and 10 replicated from previous studies. One trans-pQTL of the fucosyltransferase 2 [FUT2] gene [rs602662] and two independent cis-pQTLs of C-C motif chemokine 25 [CCL25] affected plasma CCL25 levels. Intestinal gene expression data revealed an overlapping cis-expression [e]QTL-variant [rs3745387] of the CCL25 gene. The FUT2 rs602662 trans-pQTL was associated with reduced abundances of faecal butyrate-producing bacteria.
CONCLUSIONS
CONCLUSIONS
This study shows that genotype and multiple disease phenotypes strongly associate with the plasma inflammatory proteome in IBD, and identifies disease-associated pathways that may help to improve disease management in the future.
Identifiants
pubmed: 34491321
pii: 6365883
doi: 10.1093/ecco-jcc/jjab157
pmc: PMC8919819
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
414-429Subventions
Organisme : Samenwerkende Gezondheidsfondsen
Organisme : Takeda Canada
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek
ID : 194.006
Organisme : University of Groningen
ID : 17-57
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.
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