ArticleJournal of biomedical science2017
H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.
Article in Journal of biomedical science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pooled it
- Brugada Syndrome: an exemplar for the genomic basis of sudden death.European journal of human genetics : EJHG · 2026Review
- Article
- The role of adrenaline in comprehensive management of electrical storms in high-risk Brugada syndrome with rare SCN5A mutation: a case report from medical stabilization to implantable cardioverter-defibrillator implantation.European heart journal. Case reports · 2025Article
- Article
- Review
- Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Article
- The Genetics and Epigenetics of Ventricular Arrhythmias in Patients Without Structural Heart Disease.Frontiers in cardiovascular medicine · 2022Review
- Expression defect of the rare variant/Brugada mutation R1512W depends upon the SCN5A splice variant background and can be rescued by mexiletine and the common polymorphism H558R.Channels (Austin, Tex.) · 2021Article
- Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.Human mutation · 2021Article
- Novel SCN5A variants identified in a group of Iranian Brugada syndrome patients.Functional & integrative genomics · 2021Article
- Functional Characterization of Two Novel Mutations inInternational journal of molecular sciences · 2021Article
- Elevated EZH2 in ischemic heart disease epigenetically mediates suppression of NaJournal of molecular and cellular cardiology · 2021Article
- Brugada Syndrome: Warning of a Systemic Condition?Frontiers in cardiovascular medicine · 2021Review
- A Heart Failure-AssociatedFrontiers in physiology · 2021Article
- Big Data and Atrial Fibrillation: Current Understanding and New Opportunities.Journal of cardiovascular translational research · 2020Review
- Role of Non-Coding Variants in Brugada Syndrome.International journal of molecular sciences · 2020Review
- Establishing a Framework for the Clinical Translation of Germline Findings in Precision Oncology.JNCI cancer spectrum · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA common SCN5A polymorphism H558R (c.1673 A > G, rs1805124) improves sodium channel activity in mutated channels and known to be a genetic modifier of Brugada syndrome patients (BrS). We investigated clinical manifestations and underlying mechanisms of H558R in BrS. METHODS AND
resultsWe genotyped H558R in 100 BrS (mean age 45 ± 14 years; 91 men) and 1875 controls (mean age 54 ± 18 years; 1546 men). We compared clinical parameters in BrS with and without H558R (H558R+ vs. H558R- group, N = 9 vs. 91). We also obtained right atrial sections from 30 patients during aortic aneurysm operations and compared SCN5A expression and methylation with or without H558R. H558R was less frequent in BrS than controls (9.0% vs. 19.2%, P = 0.028). The VF occurrence ratio was significantly lower (0% vs. 29.7%, P = 0.03) and spontaneous type 1 ECG was less observed in H558R+ than H558R- group (33.3% vs. 74.7%, P = 0.01). The SCN5A expression level was significantly higher and the methylation rate was significantly lower in sections with H558R (N = 10) than those without (0.98 ± 0.14 vs. 0.83 ± 0.19, P = 0.04; 0.7 ± 0.2% vs. 1.6 ± 0.1%, P = 0.004, respectively). In BrS with heterozygous H558R, the A allele mRNA expression was 1.38 fold higher than G allele expression.
conclusionThe SCN5A polymorphism H558R may be a modifier that protects against VF occurrence in BrS. The H558R decreased the SCN5A promoter methylation and increased the expression level in cardiac tissue. An allelic expression imbalance in BrS with a heterozygous H558R may also contribute to the protective effects in heterozygous mutations.
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