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.
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Shamik
authors.initials: S
authors.lastname: Polley
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Prescott
authors.affiliation: Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Nimmo
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Veal
authors.affiliation: Microbiology and Infection Control Unit, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Vind
authors.affiliation: Microbiology and Infection Control Unit, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Pia
authors.initials: P
authors.lastname: Munkholm
authors.affiliation: Microbiology and Infection Control Unit, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peder
authors.initials: P
authors.lastname: Fode
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Mansfield
authors.affiliation: Microbiology and Infection Control Unit, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Paal
authors.initials: P
authors.lastname: Skyt Andersen
authors.affiliation: Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, UK.|Sydney Brenner Institute for Molecular Bioscience, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Christopher
authors.initials: C
authors.lastname: G Mathew
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hollox
mesh_terms: D000483:Alleles; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D003545:Cysteine / Q000737:chemistry; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins; D006801:Humans; D000072417:Protein Domains; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D003545:Cysteine
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