ArticlePLoS genetics2013
Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Decreased concentration of transcription factor 21 in patients with chronic schizophrenia is associated with an increased coronary artery calcium score.BMC psychiatry · 2026Article
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- Review
- Coronary artery disease-associated variants regulate vascular smooth muscle cell gene expression.Nature cardiovascular research · 2025Article
- Article
- Computational Assessment of the Expression-modulating Potential for Non-coding Variants.Genomics, proteomics & bioinformatics · 2023Article
- TGFβ signaling pathways in human health and disease.Frontiers in molecular biosciences · 2023Review
- Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Smad3 regulates smooth muscle cell fate and mediates adverse remodeling and calcification of the atherosclerotic plaque.Nature cardiovascular research · 2022Article
- Vascular smooth muscle cells in atherosclerosis: time for a re-assessment.Cardiovascular research · 2021Review
- Serum Levels of lncRNA CCHE1 and TCF21 in Patients with Coronary Artery Disease and Their Clinical Significances.Disease markers · 2021Article
- Smooth muscle cells in atherosclerosis: clones but not carbon copies.JVS-vascular science · 2021Review
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
- Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells.Circulation research · 2020Article
- TCF21: a critical transcription factor in health and cancer.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Coronary Disease-Associated GeneCirculation research · 2020Article
- The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease.Frontiers in cell and developmental biology · 2020Review
- Genomic profiling of human vascular cells identifies TWIST1 as a causal gene for common vascular diseases.PLoS genetics · 2020Article
- CXCL12 promotes atherosclerosis by downregulating ABCA1 expression via the CXCR4/GSK3β/β-cateninJournal of lipid research · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-β) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.
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Registered trials
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.