Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia

被引:370
作者
Splawski, I
Timothy, KW
Tateyama, M
Clancy, CE
Malhotra, A
Beggs, AH
Cappuccio, FP
Sagnella, GA
Kass, RS
Keating, MT
机构
[1] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[4] Howard Hughes Med Inst, Boston, MA 02115 USA
[5] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA
[6] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA
[7] Childrens Hosp, Div Genet, Boston, MA 02115 USA
[8] Univ London St Georges Hosp, Sch Med, Dept Gen Practice & Primary Care, London SW17 0RE, England
[9] Univ London St Georges Hosp, Sch Med, Dept Med Physiol, London SW17 0RE, England
关键词
D O I
10.1126/science.1073569
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Every year, similar to450,000 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.
引用
收藏
页码:1333 / 1336
页数:5
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