Genetic variation in SCN10A influences cardiac conduction

被引：215

作者：

Chambers, John C. ^{[1
,2
]}

Zhao, Jing ^{[3
]}

Terracciano, Cesare M. N. ^{[4
]}

Bezzina, Connie R. ^{[5
,6
]}

Zhang, Weihua ^{[1
,2
]}

Kaba, Riyaz ^{[4
]}

Navaratnarajah, Manoraj ^{[4
]}

Lotlikar, Amol ^{[3
]}

Sehmi, Joban S. ^{[2
,4
]}

Kooner, Manraj K. ^{[2
,4
]}

Deng, Guohong ^{[2
,7
]}

Siedlecka, Urszula ^{[4
]}

Parasramka, Saurabh ^{[2
]}

El-Hamamsy, Ismail ^{[4
]}

Wass, Mark N. ^{[8
]}

Dekker, Lukas R. C. ^{[6
]}

de Jong, Jonas S. S. G. ^{[6
]}

Sternberg, Michael J. E. ^{[8
]}

McKenna, William ^{[9
]}

Severs, Nicholas J. ^{[4
]}

de Silva, Ranil ^{[2
,4
]}

Wilde, Arthur A. M. ^{[5
,6
]}

Anand, Praveen ^{[10
]}

Yacoub, Magdi ^{[4
]}

Scott, James ^{[4
]}

Elliott, Paul ^{[1
]}

Wood, John N. ^{[3
]}

Kooner, Jaspal S. ^{[2
,4
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England

[2] Ealing Hosp Natl Hlth Serv NHS Trust, Middlesex, England

[3] UCL, Wolfson Inst Biomed Res, London, England

[4] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England

[5] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands

[6] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands

[7] Univ London Imperial Coll Sci Technol & Med, Dept Gastroenterol & Hepatol, London, England

[8] Univ London Imperial Coll Sci Technol & Med, Struct Bioinformat Grp, London, England

[9] UCL, Inst Cardiovasc Sci, London, England

[10] Univ London Imperial Coll Sci Technol & Med, Dept Clin Neurosci, London, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 02期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

SODIUM-CHANNEL NA(V)1.8; QT INTERVAL DURATION; COMMON VARIANTS; SUDDEN-DEATH; DRG NEURONS; MORTALITY; HEART; DISEASE; BURDEN; PAIN;

D O I：

10.1038/ng.516

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：149 / U80

页数：5

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