Genetic Variation in SCN10A Influences Cardiac Conduction

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Jan 12

PMID 20062061

Citations 147

Authors

John C Chambers

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

Affiliations

Soon will be listed here.

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.

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