Human intelectin-1 (ITLN1) genetic variation and intestinal expression
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Published version
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Author(s)
Nonnecke, Eric B
Castillo, Patricia A
Dugan, Amanda E
Almalki, Faisal
Underwood, Mark A
De La Motte, Carol A
Yuan, Weirong
Lu, Wuyuan
Shen, Bo
Johansson, Malin EV
Date Issued
2021
Journal
Scientific Reports
Publisher
Springer Science and Business Media LLC
Citation
Nonnecke, Eric B, Castillo, Patricia A, Dugan, Amanda E, Almalki, Faisal, Underwood, Mark A et al. 2021. "Human intelectin-1 (ITLN1) genetic variation and intestinal expression." Scientific Reports, 11 (1).
Version
Final published version
Abstract
Intelectins 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 signifcance 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 confrm 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
infuence ITLN1 glycan binding to the glycan β-D-galactofuranose or protein–protein oligomerization.
Taken together, our data are an important step in defning 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 fndings suggest that the relationship
between the genomic data and disease arises from changes in CD244 or Ly9 biology, diferences in
ITLN1 expression in other tissues, or an alteration in ITLN1 interaction with other proteins.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/S41598-021-92198-9
