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- Title
Genetic variation in SCN10A influences cardiac conduction.
- Authors
John C. Chambers; Jing Zhao; Terracciano, Cesare M. N.; Bezzina, Connie R.; Weihua Zhang; Kaba, Riyaz; Navaratnarajah, Manoraj; Lotlikar, Amol; Sehmi, Joban S.; Kooner, Manraj K.; Guohong Deng; Siedlecka, Urszula; Parasramka, Saurabh; El-Hamamsy, Ismail; Wass, Mark N.; Dekker, Lukas R. C.; de Jong, Jonas S. S. G.; Sternberg, Michael J. E.; McKenna, William; Severs, Nicholas J.
- 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 × 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 pathogenesis of cardiac conduction, heart block and ventricular fibrillation.
- Subjects
GENOMES; LABORATORY mice; HEART block; VENTRICULAR fibrillation; HUMAN genetic variation; CORONARY disease; HEART conduction system
- Publication
Nature Genetics, 2010, Vol 42, Issue 2, p149
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.516