| First Author | Chambers JC | Year | 2010 |
| Journal | Nat Genet | Volume | 42 |
| Issue | 2 | Pages | 149-52 |
| PubMed ID | 20062061 | Mgi Jnum | J:166572 |
| Mgi Id | MGI:4848026 | Doi | 10.1038/ng.516 |
| Citation | Chambers JC, et al. (2010) Genetic variation in SCN10A influences cardiac conduction. Nat Genet 42(2):149-52 |
| abstractText | 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. |
