Human intelectin-1 (ITLN1) genetic variation and intestinal expression
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 a...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/141094 |
| _version_ | 1826205278498979840 |
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| author | 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 Kiessling, Laura L Hollox, Edward J Lönnerdal, Bo Bevins, Charles L |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry 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 Kiessling, Laura L Hollox, Edward J Lönnerdal, Bo Bevins, Charles L |
| author_sort | Nonnecke, Eric B |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:10:11Z |
| format | Article |
| id | mit-1721.1/141094 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:10:11Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1410942023-06-22T13:54:36Z Human intelectin-1 (ITLN1) genetic variation and intestinal expression 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 Kiessling, Laura L Hollox, Edward J Lönnerdal, Bo Bevins, Charles L Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT 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. 2022-03-09T17:39:51Z 2022-03-09T17:39:51Z 2021 2022-03-09T17:30:25Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141094 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). en 10.1038/S41598-021-92198-9 Scientific Reports Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Scientific Reports |
| spellingShingle | 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 Kiessling, Laura L Hollox, Edward J Lönnerdal, Bo Bevins, Charles L Human intelectin-1 (ITLN1) genetic variation and intestinal expression |
| title | Human intelectin-1 (ITLN1) genetic variation and intestinal expression |
| title_full | Human intelectin-1 (ITLN1) genetic variation and intestinal expression |
| title_fullStr | Human intelectin-1 (ITLN1) genetic variation and intestinal expression |
| title_full_unstemmed | Human intelectin-1 (ITLN1) genetic variation and intestinal expression |
| title_short | Human intelectin-1 (ITLN1) genetic variation and intestinal expression |
| title_sort | human intelectin 1 itln1 genetic variation and intestinal expression |
| url | https://hdl.handle.net/1721.1/141094 |
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