ArticleGastroenterology2013
Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Pooled it
- PRDM1-mediated epigenetic and transcriptional repression mechanisms: a key hub in immune differentiation, tumor progression, and inflammatory responses.Frontiers in immunology · 2026Review
- BLIMP-1 and CEACAM1 cooperatively regulate human Treg homeostasis and function to control xenogeneic GVHD.JCI insight · 2025Article
- [Protective effect of knock-down the expression ofBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Kurarinone ameliorates intestinal mucosal inflammation via regulating T cell immunity.Frontiers in immunology · 2025Article
- Autophagy in inflammatory bowel disease: immunization, etiology, and therapeutic potential.Frontiers in immunology · 2025Review
- Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease.Gastro hep advances · 2025Review
- Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.Nature immunology · 2024Article
- CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods.Genome biology · 2024Article
- Identification of autophagy receptors for the Crohn's disease-associated adherent-invasiveFrontiers in cellular and infection microbiology · 2024Article
- Autophagy genes in biology and disease.Nature reviews. Genetics · 2023Review
- Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription.Nature communications · 2023Article
- The genetics of non-monogenic IBD.Human genetics · 2023Review
- The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease.Biochemical Society transactions · 2023Article
- Autoimmunity and Carcinogenesis: Their Relationship under the Umbrella of Autophagy.Biomedicines · 2023Review
- Blimp-1 and c-Maf regulateWellcome open research · 2023Article
- Article
- Blimp-1 molds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit.JCI insight · 2022Article
- A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4Mucosal immunology · 2022Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
61 authors at 20 institutions in 12 countries.
Funding
Abstract
BACKGROUND &
aimsGenome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies.
methodsWe sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems.
resultsWe identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 × 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 × 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor κB activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways.
conclusionsWe have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.