| Literature DB >> 20062061 |
John C Chambers1, Jing Zhao, Cesare M N 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 R C Dekker, Jonas S S G de Jong, Michael J E Sternberg, William McKenna, Nicholas J Severs, Ranil de Silva, Arthur A M Wilde, Praveen Anand, Magdi Yacoub, James Scott, Paul Elliott, John N Wood, Jaspal S Kooner.
Abstract
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.Entities:
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Year: 2010 PMID： 20062061 DOI： 10.1038/ng.516
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330