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Variant of SCN5A Sodium Channel Implicated in Risk of Cardiac Arrhythmia

Science  23 Aug 2002:
Vol. 297, Issue 5585, pp. 1333-1336
DOI: 10.1126/science.1073569

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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.

  • * To whom correspondence should be addressed. E-mail: igor{at}enders.tch.harvard.edu (I.S.); mkeating{at}enders.tch.harvard.edu (M.T.K.)

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