ArticleThe Journal of clinical investigation2018
A common variant alters SCN5A-miR-24 interaction and associates with heart failure mortality.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Cardiac Sodium Channel Regulation: A Potential New Therapeutic Target in Cardiomyopathy.Circulation research · 2026Article
- Short SCN5A Transcript Yields a NaV1.5 Fragment Influencing Cardiac Metabolism.Circulation research · 2026Article
- Sodium Channel mRNA Binding Proteins.JACC. Basic to translational science · 2026Article
- Heritability and causality of QRS duration and chronic heart failure risk.ESC heart failure · 2025Article
- Voltage-Gated Sodium Channels: A Therapeutic Target in Ischemic Heart Disease.Reviews in cardiovascular medicine · 2025Review
- Oxidative Stress Causes Mitochondrial and Electrophysiologic Dysfunction to Promote Atrial Fibrillation inCirculation. Arrhythmia and electrophysiology · 2025Article
- Long-QT Trafficking Map.Circulation · 2024Article
- A common variant in PIK3CG gene associated with the prognosis of heart failure.Journal of cellular and molecular medicine · 2024Article
- MicroRNA-452-5p regulates fibrogenesis via targeting TGF-β/SMAD4 axis in SCN5A-knockdown human cardiac fibroblasts.iScience · 2024Article
- Mechanism of Action of NvZhen ErXian HeJi in Ovariectomized Rats with Myocardial Infarction based on Network Pharmacology.Current pharmaceutical design · 2024Article
- Modulation of miR-29 influences myocardial compliance likely through coordinated regulation of calcium handling and extracellular matrix.Molecular therapy. Nucleic acids · 2023Article
- SUMOylation of the cardiac sodium channel NaHeart rhythm · 2023Article
- Genomic approaches to identify and investigate genes associated with atrial fibrillation and heart failure susceptibility.Human genomics · 2023Review
- Multilayer control of cardiac electrophysiology by microRNAs.Journal of molecular and cellular cardiology · 2022Review
- MiR-24-3p Attenuates Doxorubicin-induced Cardiotoxicity via the Nrf2 Pathway in Mice.Current medical science · 2022Article
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Searching for genetic modulators of the phenotypic heterogeneity in Brugada syndrome.PloS one · 2022Article
- Versatile role of miR-24/24-1*/24-2* expression in cancer and other human diseases.American journal of translational research · 2022Review
- Structural and Functional Characterization of a NaCirculation research · 2021Article
- MIR448 antagomir reduces arrhythmic risk after myocardial infarction by upregulating the cardiac sodium channel.JCI insight · 2020Article
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Authors and funding
25 authors at 11 institutions in 1 country.
Funding
Abstract
SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence. This SNP was previously shown to reproducibly associate with cardiac electrophysiological parameters, but was not considered to be causal. Here, we show that miR-24 potently suppresses SCN5A expression and that rs1805126 modulates this regulation. We found that the rs1805126 minor allele associates with decreased cardiac SCN5A expression and that heart failure subjects homozygous for the minor allele have decreased ejection fraction and increased mortality, but not increased ventricular tachyarrhythmias. In mice, we identified a potential basis for this in discovering that decreased Scn5a expression leads to accumulation of myocardial reactive oxygen species. Together, these data reiterate the importance of considering the mechanistic significance of synonymous SNPs as they relate to miRs and disease, and highlight a surprising link between SCN5A expression and nonarrhythmic death in heart failure.
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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.