ArticlePloS one2013
Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 25 citations in OpenAlex.
- Multiomic spatial atlas shows deleted in malignant brain tumors 1 (DMBT1) glycoprotein is lost in colonic dysplasia.The Journal of pathology · 2025Article
- Defined Diets Link Iron and α-Linolenic Acid to Cyp1b1 Regulation of Neonatal Liver Development Through Srebp Forms and LncRNA H19.International journal of molecular sciences · 2025Article
- Balancing selection at the human salivary agglutinin gene (iScience · 2022Article
- Genetic Variants of DMBT1 and SFTPD and Disease Severity in Paediatric Inflammatory Bowel Disease-A Polish Population-Based Study.Children (Basel, Switzerland) · 2021Article
- Structure-Function Characterization of Streptococcus intermedius Surface Antigen Pas.Journal of bacteriology · 2021Article
- Identification of an IL-22-Dependent Gene Signature as a Pharmacodynamic Biomarker.International journal of molecular sciences · 2021Article
- HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells.Frontiers in immunology · 2020Article
- ATF2 and ATF7 Are Critical Mediators of Intestinal Epithelial Repair.Cellular and molecular gastroenterology and hepatology · 2020Article
- Potential Vaccines for Treating Crohn's DiseaseIranian biomedical journal · 2020Review
- Association between the rs7583431 single nucleotide polymorphism close to the activating transcription factor 2 gene and the analgesic effect of fentanyl in the cold pain test.Neuropsychopharmacology reports · 2018Article
- Genetic polymorphism in ATG16L1 gene is associated with adalimumab use in inflammatory bowel disease.Journal of translational medicine · 2017Article
- Copy number variation of scavenger-receptor cysteine-rich domains within DMBT1 and Crohn's disease.European journal of human genetics : EJHG · 2016Article
- SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces.Frontiers in immunology · 2016Review
- Intestinal neuroendocrine cells and goblet cells are mediators of IL-17A-amplified epithelial IL-17C production in human inflammatory bowel disease.Mucosal immunology · 2015Article
- Sparse Modeling Reveals miRNA Signatures for Diagnostics of Inflammatory Bowel Disease.PloS one · 2015Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesDMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression.
methodsSeven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays.
resultsIL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele.
conclusionWe identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.
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