Genetic variation in SCN10A influences cardiac conduction.
Nat Genet
; 42(2): 149-52, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-20062061
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Canais de Sódio
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Sistema de Condução Cardíaco
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
/
Europa
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido