Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia

Igor Splawski, Katherine W. Timothy, Michihiro Tateyama, Colleen E Clancy, Alka Malhotra, Alan H. Beggs, Francesco P. Cappuccio, Giuseppe A. Sagnella, Robert S. Kass, Mark T. Keating

Research output: Contribution to journalArticle

438 Citations (Scopus)

Abstract

Every year, ∼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.

Original languageEnglish (US)
Pages (from-to)1333-1336
Number of pages4
JournalScience
Volume297
Issue number5585
DOIs
StatePublished - Aug 23 2002
Externally publishedYes

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Sodium Channels
Cardiac Arrhythmias
African Americans
Alleles
Genes

ASJC Scopus subject areas

  • General

Cite this

Splawski, I., Timothy, K. W., Tateyama, M., Clancy, C. E., Malhotra, A., Beggs, A. H., ... Keating, M. T. (2002). Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science, 297(5585), 1333-1336. https://doi.org/10.1126/science.1073569

Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. / Splawski, Igor; Timothy, Katherine W.; Tateyama, Michihiro; Clancy, Colleen E; Malhotra, Alka; Beggs, Alan H.; Cappuccio, Francesco P.; Sagnella, Giuseppe A.; Kass, Robert S.; Keating, Mark T.

In: Science, Vol. 297, No. 5585, 23.08.2002, p. 1333-1336.

Research output: Contribution to journalArticle

Splawski, I, Timothy, KW, Tateyama, M, Clancy, CE, Malhotra, A, Beggs, AH, Cappuccio, FP, Sagnella, GA, Kass, RS & Keating, MT 2002, 'Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia', Science, vol. 297, no. 5585, pp. 1333-1336. https://doi.org/10.1126/science.1073569
Splawski I, Timothy KW, Tateyama M, Clancy CE, Malhotra A, Beggs AH et al. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002 Aug 23;297(5585):1333-1336. https://doi.org/10.1126/science.1073569
Splawski, Igor ; Timothy, Katherine W. ; Tateyama, Michihiro ; Clancy, Colleen E ; Malhotra, Alka ; Beggs, Alan H. ; Cappuccio, Francesco P. ; Sagnella, Giuseppe A. ; Kass, Robert S. ; Keating, Mark T. / Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. In: Science. 2002 ; Vol. 297, No. 5585. pp. 1333-1336.
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