ArticleNature communications2022
A non-coding GWAS variant impacts anthracycline-induced cardiotoxic phenotypes in human iPSC-derived cardiomyocytes.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
11 citing papers in PubMed, 12 citations in OpenAlex.
- Genetic and Molecular Determinants of Cancer Therapy-Related Cardiovascular Toxicity.Cardiovascular toxicology · 2026Review
- Multidimensional perspectives on cancer therapy-induced cardiotoxicity: Characteristics, mechanisms, biomarkers, psychological stress effects, and treatment progress.Cancer pathogenesis and therapy · 2026Review
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- Transcriptional regulatory network analysis uncovers modular gene control and potential key regulators in diabetic cardiomyopathy.Frontiers in cell and developmental biology · 2026Article
- Understanding the Mechanisms of Chemotherapy-Related Cardiotoxicity Employing hiPSC-Derived Cardiomyocyte Models for Drug Screening and the Identification of Genetic and Epigenetic Variants.International journal of molecular sciences · 2025Review
- Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models.Stem cell reports · 2025Review
- Inflammation in Chemotherapy-Induced Cardiotoxicity.Current cardiology reports · 2024Review
- Review
- Novel molecular mechanisms of doxorubicin cardiotoxicity: latest leading-edge advances and clinical implications.Molecular and cellular biochemistry · 2024Review
- Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024Review
- Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Anthracyclines, widely used to treat breast cancer, have the potential for cardiotoxicity. We have previously identified and validated a germline single nucleotide polymorphism, rs28714259, associated with an increased risk of anthracycline-induced heart failure. We now provide insights into the mechanism by which rs28714259 might confer increased risk of cardiac damage. Using hiPSC-derived cardiomyocyte cell lines with either intrinsic polymorphism or CRISPR-Cas9-mediated deletion of rs28714259 locus, we demonstrate that glucocorticoid receptor signaling activated by dexamethasone pretreatment prior to doxorubicin exposure preserves cardiomyocyte viability and contractility in cardiomyocytes containing the major allele. Homozygous loss of the rs28714259 major allele diminishes dexamethasone's protective effect. We further demonstrate that the risk allele of rs28714259 disrupts glucocorticoid receptor and rs28714259 binding affinity. Finally, we highlight the activation of genes and pathways involved in cardiac hypertrophy signaling that are blocked by the risk allele, suggesting a decreased adaptive survival response to doxorubicin-related stress.
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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.