作者
John C Chambers, Jing Zhao, Cesare MN Terracciano, Connie R Bezzina, Weihua Zhang, Riyaz Kaba, Manoraj Navaratnarajah, Amol Lotlikar, Joban S Sehmi, Manraj K Kooner, Guohong Deng, Urszula Siedlecka, Saurabh Parasramka, Ismail El-Hamamsy, Mark N Wass, Lukas RC Dekker, Jonas SSG de Jong, Michael JE Sternberg, William McKenna, Nicholas J Severs, Ranil de Silva, Arthur AM Wilde, Praveen Anand, Magdi Yacoub, James Scott, Paul Elliott, John N Wood, Jaspal S Kooner
发表日期
2010/2
期刊
Nature genetics
卷号
42
期号
2
页码范围
149-152
出版商
Nature Publishing Group US
简介
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 × 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 NaV1.8, 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 …
引用总数
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JC Chambers, J Zhao, CMN Terracciano, CR Bezzina… - Nature genetics, 2010