Human intelectin-1 (ITLN1) genetic variation and intestinal expression
AuthorNonnecke, Eric B
Castillo, Patricia A
Dugan, Amanda E
Underwood, Mark A
De La Motte, Carol A
Johansson, Malin E V
Kiessling, Laura L
Hollox, Edward J
Bevins, Charles L
MetadataShow full item record
AbstractIntelectins are ancient carbohydrate binding proteins, spanning chordate evolution and implicated in multiple human diseases. Previous GWAS have linked SNPs in ITLN1 (also known as omentin) with susceptibility to Crohn's disease (CD); however, analysis of possible functional significance of SNPs at this locus is lacking. Using the Ensembl database, pairwise linkage disequilibrium (LD) analyses indicated that several disease-associated SNPs at the ITLN1 locus, including SNPs in CD244 and Ly9, were in LD. The alleles comprising the risk haplotype are the major alleles in European (67%), but minor alleles in African superpopulations. Neither ITLN1 mRNA nor protein abundance in intestinal tissue, which we confirm as goblet-cell derived, was altered in the CD samples overall nor when samples were analyzed according to genotype. Moreover, the missense variant V109D does not influence ITLN1 glycan binding to the glycan β-D-galactofuranose or protein-protein oligomerization. Taken together, our data are an important step in defining the role(s) of the CD-risk haplotype by determining that risk is unlikely to be due to changes in ITLN1 carbohydrate recognition, protein oligomerization, or expression levels in intestinal mucosa. Our findings suggest that the relationship between the genomic data and disease arises from changes in CD244 or Ly9 biology, differences in ITLN1 expression in other tissues, or an alteration in ITLN1 interaction with other proteins.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16082
- Characterization of an intelectin-1 (Itln1) knockout mouse model.
- Authors: Nonnecke EB, Castillo PA, Akahoshi DT, Goley SM, Bevins CL, Lönnerdal B
- Issue date: 2022
- Human intelectin-2 (ITLN2) is selectively expressed by secretory Paneth cells.
- Authors: Nonnecke EB, Castillo PA, Johansson MEV, Hollox EJ, Shen B, Lönnerdal B, Bevins CL
- Issue date: 2022 Mar
- Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).
- Authors: Durães C, Machado JC, Portela F, Rodrigues S, Lago P, Cravo M, Ministro P, Marques M, Cremers I, Freitas J, Cotter J, Tavares L, Matos L, Medeiros I, Sousa R, Ramos J, Deus J, Caldeira P, Chagas C, Duarte MA, Gonçalves R, Loureiro R, Barros L, Bastos I, Cancela E, Moraes MC, Moreira MJ, Vieira AI, Magro F
- Issue date: 2013 Feb
- Extensive variation in the intelectin gene family in laboratory and wild mouse strains.
- Authors: Almalki F, Nonnecke EB, Castillo PA, Bevin-Holder A, Ullrich KK, Lönnerdal B, Odenthal-Hesse L, Bevins CL, Hollox EJ
- Issue date: 2021 Jul 30
- Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer.
- Authors: Li D, Zhao X, Xiao Y, Mei H, Pu J, Xiang X, Jiao W, Song H, Qu H, Huang K, Zheng L, Tong Q
- Issue date: 2015 Jun 30