Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease

Shamik Polley; Natalie Prescott; Elaine Nimmo; Colin Veal; Ida Vind; Pia Munkholm; Peder Fode; John Mansfield; Paal Skytt Andersen; Jack Satsangi; Christopher G. Mathew; Edward J. Hollox

doi:10.1038/ejhg.2015.280

Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease

Shamik Polley, Natalie Prescott, Elaine Nimmo, Colin Veal, Ida Vind, Pia Munkholm, Peder Fode, John Mansfield, Paal Skytt Andersen, Jack Satsangi, Christopher G. Mathew, Edward J. Hollox

5 Citations (Scopus)

Abstract

Previous work has shown that the gene DMBT1, which encodes a large secreted epithelial glycoprotein known as salivary agglutinin, gp340, hensin or muclin, is an innate immune defence protein that binds bacteria. A deletion variant of DMBT1 has been previously associated with Crohn's disease, and a DMBT1(-/-) knockout mouse has increased levels of colitis induced by dextran sulphate. DMBT1 has a complex copy number variable structure, with two, independent, rapidly mutating copy number variable regions, called CNV1 and CNV2. Because the copy number variable regions are predicted to affect the number of bacteria-binding domains, different alleles may alter host-microbe interactions in the gut. Our aim was to investigate the role of this complex variation in susceptibility to Crohn's disease by assessing the previously reported association. We analysed the association of both copy number variable regions with presence of Crohn's disease, and its severity, on three case-control cohorts. We also reanalysed array comparative genomic hybridisation data (aCGH) from a large case-control cohort study for both copy number variable regions. We found no association with a linear increase in copy number, nor when the CNV1 is regarded as presence or absence of a deletion allele. Taken together, we show that the DMBT1 CNV does not affect susceptibility to Crohn's disease, at least in Northern Europeans.

Original language	English
Journal	European Journal of Human Genetics
Volume	24
Issue number	9
Pages (from-to)	1294-1300
Number of pages	7
ISSN	1018-4813
DOIs	https://doi.org/10.1038/ejhg.2015.280
Publication status	Published - 1 Aug 2016
Externally published	Yes

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Journal Article

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10.1038/ejhg.2015.280Licence: CC BY

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title = "Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease",

abstract = "Previous work has shown that the gene DMBT1, which encodes a large secreted epithelial glycoprotein known as salivary agglutinin, gp340, hensin or muclin, is an innate immune defence protein that binds bacteria. A deletion variant of DMBT1 has been previously associated with Crohn's disease, and a DMBT1(-/-) knockout mouse has increased levels of colitis induced by dextran sulphate. DMBT1 has a complex copy number variable structure, with two, independent, rapidly mutating copy number variable regions, called CNV1 and CNV2. Because the copy number variable regions are predicted to affect the number of bacteria-binding domains, different alleles may alter host-microbe interactions in the gut. Our aim was to investigate the role of this complex variation in susceptibility to Crohn's disease by assessing the previously reported association. We analysed the association of both copy number variable regions with presence of Crohn's disease, and its severity, on three case-control cohorts. We also reanalysed array comparative genomic hybridisation data (aCGH) from a large case-control cohort study for both copy number variable regions. We found no association with a linear increase in copy number, nor when the CNV1 is regarded as presence or absence of a deletion allele. Taken together, we show that the DMBT1 CNV does not affect susceptibility to Crohn's disease, at least in Northern Europeans.",

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author = "Shamik Polley and Natalie Prescott and Elaine Nimmo and Colin Veal and Ida Vind and Pia Munkholm and Peder Fode and John Mansfield and Andersen, {Paal Skytt} and Jack Satsangi and Mathew, {Christopher G.} and Hollox, {Edward J.}",

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AU - Polley, Shamik

AU - Prescott, Natalie

AU - Nimmo, Elaine

AU - Veal, Colin

AU - Vind, Ida

AU - Munkholm, Pia

AU - Fode, Peder

AU - Mansfield, John

AU - Andersen, Paal Skytt

AU - Satsangi, Jack

AU - Mathew, Christopher G.

AU - Hollox, Edward J.

PY - 2016/8/1

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N2 - Previous work has shown that the gene DMBT1, which encodes a large secreted epithelial glycoprotein known as salivary agglutinin, gp340, hensin or muclin, is an innate immune defence protein that binds bacteria. A deletion variant of DMBT1 has been previously associated with Crohn's disease, and a DMBT1(-/-) knockout mouse has increased levels of colitis induced by dextran sulphate. DMBT1 has a complex copy number variable structure, with two, independent, rapidly mutating copy number variable regions, called CNV1 and CNV2. Because the copy number variable regions are predicted to affect the number of bacteria-binding domains, different alleles may alter host-microbe interactions in the gut. Our aim was to investigate the role of this complex variation in susceptibility to Crohn's disease by assessing the previously reported association. We analysed the association of both copy number variable regions with presence of Crohn's disease, and its severity, on three case-control cohorts. We also reanalysed array comparative genomic hybridisation data (aCGH) from a large case-control cohort study for both copy number variable regions. We found no association with a linear increase in copy number, nor when the CNV1 is regarded as presence or absence of a deletion allele. Taken together, we show that the DMBT1 CNV does not affect susceptibility to Crohn's disease, at least in Northern Europeans.

AB - Previous work has shown that the gene DMBT1, which encodes a large secreted epithelial glycoprotein known as salivary agglutinin, gp340, hensin or muclin, is an innate immune defence protein that binds bacteria. A deletion variant of DMBT1 has been previously associated with Crohn's disease, and a DMBT1(-/-) knockout mouse has increased levels of colitis induced by dextran sulphate. DMBT1 has a complex copy number variable structure, with two, independent, rapidly mutating copy number variable regions, called CNV1 and CNV2. Because the copy number variable regions are predicted to affect the number of bacteria-binding domains, different alleles may alter host-microbe interactions in the gut. Our aim was to investigate the role of this complex variation in susceptibility to Crohn's disease by assessing the previously reported association. We analysed the association of both copy number variable regions with presence of Crohn's disease, and its severity, on three case-control cohorts. We also reanalysed array comparative genomic hybridisation data (aCGH) from a large case-control cohort study for both copy number variable regions. We found no association with a linear increase in copy number, nor when the CNV1 is regarded as presence or absence of a deletion allele. Taken together, we show that the DMBT1 CNV does not affect susceptibility to Crohn's disease, at least in Northern Europeans.

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DO - 10.1038/ejhg.2015.280

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JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

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ER -

Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease

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