Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
SIDS: genetic and environmental influences may cause arrhythmia in this silent killer
Jonathan C. Makielski
Jonathan C. Makielski
Published February 1, 2006
Citation Information: J Clin Invest. 2006;116(2):297-299. https://doi.org/10.1172/JCI27689.
View: Text | PDF
Commentary

SIDS: genetic and environmental influences may cause arrhythmia in this silent killer

  • Text
  • PDF
Abstract

In this issue of the JCI, Bowers et al. show that the common polymorphism of the cardiac voltage-gated sodium channel, type Vα (SCN5A), designated S1103Y, found in African Americans is associated with an increased risk of sudden infant death syndrome (SIDS). Wild-type and mutant SCN5A channels both functioned typically under normal conditions in vitro, but exposure to acidic intracellular pH levels such as those found in respiratory acidosis — a known risk factor for SIDS — produced abnormal gain-of-function late reopenings of S1103Y channels, behavior that is often associated with cardiac arrhythmias. These pathologic late reopenings were suppressed by low levels of the channel-blocking drug mexiletine. These findings provide an excellent illustration of a causal relationship between the interaction of the environment and genetic background in SIDS and also raise interesting questions about the linkage of a genetic abnormality with a clinical phenotype.

Authors

Jonathan C. Makielski

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
An arrhythmogenic pathogenetic pathway for SIDS from patient genotype to...
An arrhythmogenic pathogenetic pathway for SIDS from patient genotype to clinical phenotype. The figure denotes the pathogenic pathway from genotype to clinical phenotype, with environmental influences noted. The genetic abnormality, in this instance a polymorphism in the cardiac Na+ channel SCN5A, causes a molecular phenotype of increased late Na+ current (INa) under the influence of environmental factors such as acidosis. Interacting with other ion currents that may themselves be altered by genetic and environmental factors, the late Na+ current causes a cellular phenotype of prolonged action potential duration as well as early afterdepolarizations. Prolonged action potential in the cells of the ventricular myocardium and further interaction with environmental factors such as autonomic innervation, which in turn may be affected by genetic factors, produce a tissue/organ phenotype of a prolonged QT interval on the ECG and torsade de pointes arrhythmia in the whole heart. If this is sustained or degenerates to ventricular fibrillation, the clinical phenotype of SIDS results. Environmental and multiple genetic factors may interact at many different levels to produce the characteristic phenotypes at the molecular, cellular, tissue, organ, and clinical levels. The study by Bowers et al. in this issue of the JCI (8) demonstrates the importance of environmental influences, in this case acidosis, in the pathogenetic pathway of SIDS.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts