ArticlePloS one2009
Genetic variants of Wnt transcription factor TCF-4 (TCF7L2) putative promoter region are associated with small intestinal Crohn's disease.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 135 citations in OpenAlex.
- Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin.Archives of dermatological research · 2019Trial
- Notoginsenoside R1 promotes Lgr5Acta pharmacologica Sinica · 2024Article
- Article
- Genome-wide cross-disease analyses highlight causality and shared biological pathways of type 2 diabetes with gastrointestinal disorders.Communications biology · 2024Article
- Causal linkage between type 2 diabetes mellitus and inflammatory bowel disease: an integrated Mendelian randomization study and bioinformatics analysis.Frontiers in endocrinology · 2024Article
- Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization.Cell host & microbe · 2023Article
- Human α-Defensin 5International journal of molecular sciences · 2023Article
- Review
- Crohn's disease: Why the ileum?World journal of gastroenterology · 2023Review
- IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence.Nature communications · 2022Article
- Implication of Intestinal Barrier Dysfunction in Gut Dysbiosis and Diseases.Biomedicines · 2022Review
- Integrity of the Intestinal Barrier: The Involvement of Epithelial Cells and Microbiota-A Mutual Relationship.Animals : an open access journal from MDPI · 2022Review
- The broad pathogenetic role of TCF7L2 in human diseases beyond type 2 diabetes.Journal of cellular physiology · 2022Review
- Roles of MicroRNAs in Osteogenesis or Adipogenesis Differentiation of Bone Marrow Stromal Progenitor Cells.International journal of molecular sciences · 2021Review
- The roles and functions of Paneth cells in Crohn's disease: A critical review.Cell proliferation · 2021Review
- Article
- The MYTHS ofJapanese journal of gastroenterology and hepatology · 2020Article
- An Update Review on the Paneth Cell as Key to Ileal Crohn's Disease.Frontiers in immunology · 2020Review
- Intestinal Epithelial Wnt Signaling Mediates Acetylcholine-Triggered Host Defense against Infection.Immunity · 2018Article
- Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice.Disease models & mechanisms · 2018Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 9 institutions in 8 countries.
Funding
Abstract
Reduced expression of Paneth cell antimicrobial alpha-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.1 kb of the 5' flanking region of TCF-4 in a small group of ileal CD patients and controls (n = 10 each). We identified eight single nucleotide polymorphisms (SNPs), of which three (rs3814570, rs10885394, rs10885395) were in linkage disequilibrium and found more frequently in patients; one (rs3814570) was thereby located in a predicted regulatory region. We carried out high-throughput analysis of this SNP in three cohorts of inflammatory bowel disease (IBD) patients and controls. Overall 1399 healthy individuals, 785 ulcerative colitis (UC) patients, 225 CD patients with colonic disease only and 784 CD patients with ileal involvement were used to determine frequency distributions. We found an association of rs3814570 with ileal CD but neither with colonic CD or UC, in a combined analysis (allele positivity: OR 1.27, 95% CI 1.07 to 1.52, p = 0.00737), which was the strongest in ileal CD patients with stricturing behaviour (allele frequency: OR 1.32, 95% CI 1.08 to1.62, p = 0.00686) or an additional involvement of the upper GIT (allele frequency: OR 1.38, 95% CI 1.03 to1.84, p = 0.02882). The newly identified genetic association of TCF-4 with ileal CD provides evidence that the decrease in Paneth cell alpha-defensins is a primary factor in disease pathogenesis.
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