Genetic variation in SCN10A influences cardiac conduction

Chambers, John C and Zhao, Jing and Terracciano, Cesare M.N. and Bezzina, Connie R. and Zhang, Weihua and Kaba, Riyaz and Navaratnarajah, Manoraj and Lotlikar, Amol and Sehmi, Joban S. and Kooner, Manraj K. and Deng, Guohong and Siedlecka, Urszula and Parasramka, Saurabh and El-Hamamsy, Ismail and Wass, Mark N. and Dekker, Lukas R.C. and de Jong, Jonas S.S.G. and Sternberg, Michael J.E. and McKenna, William and Severs, Nicholas J and de Silva, Ranil and Wilde, Arthur A.M. and Anand, Praveen and Yacoub, Magdi H. and Scott, James and Elliott, Paul and Wood, John N. and Kooner, Jaspal S (2010) Genetic variation in SCN10A influences cardiac conduction. Nature Genetics, 42 (2). pp. 149-152. ISSN 1546-1718. (doi:https://doi.org/10.1038/ng.516) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1038/ng.516

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.

Item Type: Article
Subjects: Q Science
R Medicine
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Mark Wass
Date Deposited: 06 Jun 2013 13:23 UTC
Last Modified: 06 Jun 2017 11:12 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/34181 (The current URI for this page, for reference purposes)
ORCiD (Wass, Mark N.): http://orcid.org/0000-0001-5428-6479
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