| Genetic variation in SCN10A influences cardiac conduction. | |
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MedLine Citation:
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PMID: 20062061 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-10 |
Journal Detail:
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Title: Nature genetics Volume: 42 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-27 Completed Date: 2010-02-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 149-52 Citation Subset: IM |
Affiliation:
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Department of Epidemiology and Public Health, Imperial College London, UK. john.chambers@ic.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Animals Asian Continental Ancestry Group / genetics Chromosomes, Human, Pair 3 / genetics Electrocardiography Europe Female 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 Humans India Male Mice Middle Aged Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide / genetics Reproducibility of Results Sodium Channels / deficiency, genetics* Telemetry Ventricular Fibrillation / complications, genetics, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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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; SP/04/002//British Heart Foundation |
| Chemical | |
Reg. No./Substance:
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0/Sodium Channels; 0/sensory neuron specific (SNS) sodium channel |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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