Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia

Science. 2002 Aug 23;297(5585):1333-6. doi: 10.1126/science.1073569.

Abstract

Every year, approximately 450,000 individuals in the United States die suddenly of cardiac arrhythmia. We identified a variant of the cardiac sodium channel gene SCN5A that is associated with arrhythmia in African Americans (P = 0.000028) and linked with arrhythmia risk in an African-American family (P = 0.005). In transfected cells, the variant allele (Y1102) accelerated channel activation, increasing the likelihood of abnormal cardiac repolarization and arrhythmia. About 13.2% of African Americans carry the Y1102 allele. Because Y1102 has a subtle effect on risk, most carriers will never have an arrhythmia. However, Y1102 may be a useful molecular marker for the prediction of arrhythmia susceptibility in the context of additional acquired risk factors such as the use of certain medications.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Amino Acid Sequence
  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / genetics*
  • Black People / genetics*
  • Case-Control Studies
  • Cell Line
  • Child
  • Electrocardiography
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Humans
  • Ion Channel Gating
  • Long QT Syndrome / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • NAV1.5 Voltage-Gated Sodium Channel
  • Patch-Clamp Techniques
  • Pedigree
  • Point Mutation*
  • Polymorphism, Single-Stranded Conformational
  • Probability
  • Risk Factors
  • Sodium Channels / chemistry
  • Sodium Channels / genetics*
  • Sodium Channels / metabolism
  • Syncope
  • Transfection

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels