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Genetic variation in SCN10A influences cardiac conduction

Chambers, JC; Zhao, J; Terracciano, CMN; Bezzina, CR; Zhang, WH; Kaba, R; Navaratnarajah, M; ... Kooner, JS; + view all (2010) Genetic variation in SCN10A influences cardiac conduction. NAT GENET , 42 (2) 149 - U80. 10.1038/ng.516.

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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.

Type: Article
Title: Genetic variation in SCN10A influences cardiac conduction
DOI: 10.1038/ng.516
Keywords: SODIUM-CHANNEL NA(V)1.8, QT INTERVAL DURATION, COMMON VARIANTS, SUDDEN-DEATH, DRG NEURONS, MORTALITY, HEART, DISEASE, BURDEN, PAIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
URI: http://discovery.ucl.ac.uk/id/eprint/128560
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