Document Detail

Genetic variation in SCN10A influences cardiac conduction.
MedLine Citation:
PMID:  20062061     Owner:  NLM     Status:  MEDLINE    
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.
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-10
Journal Detail:
Title:  Nature genetics     Volume:  42     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-02-17     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  149-52     Citation Subset:  IM    
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MeSH Terms
Asian Continental Ancestry Group / genetics
Chromosomes, Human, Pair 3 / genetics
Genetic Loci / genetics
Genetic Predisposition to Disease
Genetic Variation*
Genome-Wide Association Study
Heart Block / complications,  genetics,  physiopathology
Heart Conduction System / physiology*
Heart Rate / genetics
Middle Aged
NAV1.8 Voltage-Gated Sodium Channel
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide / genetics
Reproducibility of Results
Sodium Channels / deficiency,  genetics*
Ventricular Fibrillation / complications,  genetics,  physiopathology
Grant Support
084723/Z/08/Z//Wellcome Trust; BB/F000227/1//Biotechnology and Biological Sciences Research Council; BB/F020481/1//Biotechnology and Biological Sciences Research Council; F/99089//British Heart Foundation; G0601966//Medical Research Council; G0700931//Medical Research Council; G0801056//Medical Research Council; G0901905//Medical Research Council; G9717869//Medical Research Council; SP/04/002//British Heart Foundation
Reg. No./Substance:
0/NAV1.8 Voltage-Gated Sodium Channel; 0/SCN10A protein, human; 0/Scn10a protein, mouse; 0/Sodium Channels

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