Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction

被引：124

作者：

Bezzina, Connie R. ^{[1
]}

Pazoki, Raha ^{[1
,2
]}

Bardai, Abdennasser ^{[1
]}

Marsman, Roos F. ^{[1
]}

de Jong, Jonas S. S. G. ^{[3
]}

Blom, Marieke T. ^{[1
]}

Scicluna, Brendon P. ^{[1
]}

Jukema, J. Wouter ^{[4
,5
]}

Bindraban, Navin R. ^{[3
,6
]}

Lichtner, Peter ^{[7
]}

Pfeufer, Arne ^{[7
,8
]}

Bishopric, Nanette H. ^{[9
,10
,11
]}

Roden, Dan M. ^{[12
]}

Meitinger, Thomas ^{[7
,8
]}

Chugh, Sumeet S. ^{[13
]}

Myerburg, Robert J. ^{[9
]}

Jouven, Xavier ^{[14
]}

Kaab, Stefan ^{[15
]}

Dekker, Lukas R. C. ^{[3
,16
]}

Tan, Hanno L. ^{[1
,3
]}

Tanck, Michael W. T. ^{[2
]}

Wilde, Arthur A. M. ^{[1
,3
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Expt Cardiol, Heart Failure Res Ctr, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, NL-1105 AZ Amsterdam, Netherlands

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

[4] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands

[5] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands

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

[7] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany

[8] Deutsch Forschungszentrum Gesundheit & Umwelt, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[9] Univ Miami, Miller Sch Med, Dept Med, Div Cardiol, Miami, FL 33136 USA

[10] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA

[11] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA

[12] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA

[13] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA

[14] Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, Paris, France

[15] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany

[16] Catharina Hosp, Dept Cardiol, Eindhoven, Netherlands

来源：

NATURE GENETICS | 2010年 / 42卷 / 08期

关键词：

SUDDEN CARDIAC DEATH; QT INTERVAL DURATION; COMMON VARIANTS; RISK-FACTOR; CARDIOMYOPATHY; ADENOVIRUSES; NETHERLANDS; DISRUPTION; SEQUENCES; GENETICS;

D O I：

10.1038/ng.623

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at 21q21 (rs2824292, odds ratio = 1.78, 95% CI 1.47-2.13, P = 3.3 x 10(-10)). The association of rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (controls) (odds ratio = 1.49, 95% CI 1.14-1.95, P = 0.004). The closest gene to this SNP is CXADR, which encodes a viral receptor previously implicated in myocarditis and dilated cardiomyopathy and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.

引用

页码：688 / U64

页数：5

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