The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease. (7th September 2021)

• Record Type: Journal Article
• Authors: Bourgonje, Arno R; Hu, Shixian; Spekhorst, Lieke M; Zhernakova, Daria V; Vich Vila, Arnau; Li, Yanni; Voskuil, Michiel D; van Berkel, Lisette A; Bley Folly, Brenda; Charrout, Mohammed; Mahfouz, Ahmed; Reinders, Marcel J T; van Heck, Julia I P; Joosten, Leo A B; Visschedijk, Marijn C; van Dullemen, Hendrik M; Faber, Klaas Nico; Samsom, Janneke N; Festen, Eleonora A M; Dijkstra, Gerard; Weersma, Rinse K
• Is Part Of: Journal of Crohn's and colitis. Volume 16:Number 3(2022)
• Page Start: 414
• Page End: 429
• Publication Date: 2021-09-07
• Subjects: Inflammatory bowel disease -- genetics -- proteomics; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjab157
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: 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: 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: 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: 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.