ArticleAmerican heart journal2014
Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT interval prolongation in African Americans: the Jackson Heart Study.
Article in American heart journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Genome-Wide Interaction Analyses of Serum Calcium on Ventricular Repolarization Time in 125 393 Participants.Journal of the American Heart Association · 2024Pooled it
- Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.The pharmacogenomics journal · 2018Pooled it
- A novel gain-of-function mutationAmerican journal of cardiovascular disease · 2025Article
- Clinical and Laboratory Correlates of QTc Duration in Adult and Pediatric Sickle Cell Disease.American journal of medicine open · 2023Article
- Common Ancestry-Specific Ion Channel Variants Predispose to Drug-Induced Arrhythmias.Circulation · 2022Article
- Article
- Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors: A Pharmacovigilance Study.Frontiers in endocrinology · 2021Article
- Absence of relevant QT interval prolongation in not critically ill COVID-19 patients.Scientific reports · 2020Article
- Genetic susceptibility for COVID-19-associated sudden cardiac death in African Americans.Heart rhythm · 2020Review
- An African loss-of-function CACNA1C variant p.T1787M associated with a risk of ventricular fibrillation.Scientific reports · 2018Article
- Classification and Reporting of Potentially Proarrhythmic Common Genetic Variation in Long QT Syndrome Genetic Testing.Circulation · 2018Review
- Predictive Value of TFrontiers in physiology · 2018Article
- Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy.Journal of clinical laboratory analysis · 2017Article
- Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts.PloS one · 2014Article
- Racial differences in sudden cardiac death.Journal of electrocardiologyArticle
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAfrican-American ancestry, hypokalemia, and QT interval prolongation on the electrocardiogram are all risk factors for sudden cardiac death (SCD), but their interactions remain to be characterized. SCN5A-1103Y is a common missense variant, of African ancestry, of the cardiac sodium channel gene. SCN5A-1103Y is known to interact with QT-prolonging factors to promote ventricular arrhythmias in persons at high risk for SCD, but its clinical impact in the general African-American population has not been established.
methodsWe genotyped SCN5A-S1103Y in 4,476 participants of the Jackson Heart Study, a population-based cohort of African Americans. We investigated the effect of SCN5A-1103Y, including interaction with hypokalemia, on QT interval prolongation, a widely-used indicator of prolonged myocardial repolarization and predisposition to SCD. We then evaluated the two sub-components of the QT interval: QRS duration and JT interval.
resultsThe carrier frequency for SCN5A-1103Y was 15.4%. SCN5A-1103Y was associated with QT interval prolongation (2.7 milliseconds; P < .001) and potentiated the effect of hypokalemia on QT interval prolongation (14.6 milliseconds; P = .02). SCN5A-1103Y had opposing effects on the two sub-components of the QT interval, with shortening of QRS duration (-1.5 milliseconds; P = .001) and prolongation of the JT interval (3.4 milliseconds; P < .001). Hypokalemia was associated with diuretic use (78%; P < .001).
conclusionsSCN5A-1103Y potentiates the effect of hypokalemia on prolonging myocardial repolarization in the general African-American population. These findings have clinical implications for modification of QT prolonging factors, such as hypokalemia, in the 15% of African Americans who are carriers of SCN5A-1103Y.
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