Variant of SCN5A Sodium Channel Implicated in Risk of Cardiac Arrhythmia

TLDR

Every year, about 450,000 U.S. individuals die suddenly from cardiac arrhythmia. The study aims to evaluate Y1102 as a molecular marker for predicting arrhythmia susceptibility alongside other risk factors. In transfected cells, the Y1102 variant accelerates channel activation, heightening abnormal repolarization and arrhythmia risk.

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.