Genetic variation in SCN10A influences cardiac conduction
Genetic variation in SCN10A influences cardiac conduction
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DOI：
10.1038/ng.516
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发表时间：
2010-02-01
期刊：
影响因子：
30.8
通讯作者：
Kooner, Jaspal S.
中科院分区：
文献类型：
--
作者：
Chambers, John C.;Zhao, Jing;Kooner, Jaspal S.
为了确定影响心脏传导的遗传因素，我们对6，543名印度亚洲人进行了心电图时间间隔的全基因组关联研究。我们发现SCN 10A中的一个非同义SNP rs6795970（P = 2.8 x 10（-15））与PR间期（心脏房室传导的标志物）相关。在6，243名印度亚洲人和5，370名欧洲人中进行的重复测试证实，rs6795970（G>A）与延长的心脏传导（较长的P波持续时间，PR间期和QRS持续时间，P = 10（-5）至10（-20））相关。SCN 10A编码Na（V）1.8，一种钠通道。我们发现，SCN 10A在小鼠和人类心脏组织中表达，并且Scn 10a（-/-）小鼠的PR间期比野生型小鼠短。我们还发现rs6795970与心脏传导阻滞的风险较高（P < 0.05）和室颤的风险较低（P = 0.01）相关。我们的发现为心脏传导、心脏传导阻滞和心室颤动的发病机制提供了新的见解。
To identify genetic factors influencing cardiac conduction, we carried out a genome-wide association study of electrocardiographic time intervals in 6,543 Indian Asians. We identified association of a nonsynonymous SNP, rs6795970, in SCN10A (P = 2.8 x 10(-15)) with PR interval, a marker of cardiac atrioventricular conduction. Replication testing among 6,243 Indian Asians and 5,370 Europeans confirmed that rs6795970 (G>A) is associated with prolonged cardiac conduction (longer P-wave duration, PR interval and QRS duration, P = 10(-5) to 10(-20)). SCN10A encodes Na(V)1.8, a sodium channel. We show that SCN10A is expressed in mouse and human heart tissue and that PR interval is shorter in Scn10a(-/-) mice than in wild-type mice. We also find that rs6795970 is associated with a higher risk of heart block (P < 0.05) and a lower risk of ventricular fibrillation (P = 0.01). Our findings provide new insight into the pathogenesis of cardiac conduction, heart block and ventricular fibrillation.