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dc.contributor.authorNonnecke, Eric B
dc.contributor.authorCastillo, Patricia A
dc.contributor.authorDugan, Amanda E
dc.contributor.authorAlmalki, Faisal
dc.contributor.authorUnderwood, Mark A
dc.contributor.authorDe La Motte, Carol A
dc.contributor.authorYuan, Weirong
dc.contributor.authorLu, Wuyuan
dc.contributor.authorShen, Bo
dc.contributor.authorJohansson, Malin E V
dc.contributor.authorKiessling, Laura L
dc.contributor.authorHollox, Edward J
dc.contributor.authorLönnerdal, Bo
dc.contributor.authorBevins, Charles L
dc.date.accessioned2021-06-24T18:44:27Z
dc.date.available2021-06-24T18:44:27Z
dc.date.issued2021-06-18
dc.identifier.urihttp://hdl.handle.net/10713/16082
dc.description.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.en_US
dc.description.urihttps://doi.org/10.1038/s41598-021-92198-9en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofScientific Reportsen_US
dc.subject.meshColonen_US
dc.subject.meshCrohn Disease--geneticsen_US
dc.subject.meshPolymorphism, Single Nucleotideen_US
dc.subject.meshRisk Factorsen_US
dc.titleHuman intelectin-1 (ITLN1) genetic variation and intestinal expressionen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-021-92198-9
dc.identifier.pmid34145348
dc.source.volume11
dc.source.issue1
dc.source.beginpage12889
dc.source.endpage
dc.source.countryUnited States
dc.source.countryEngland


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