A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization

被引：397

作者：

Arking, Dan E.

Pfeufer, Arne

Post, Wendy

Kao, W. H. Linda

Newton-Cheh, Christopher

Ikeda, Morna

West, Kristen

Kashuk, Carl

Akyol, Mahmut

Perz, Siegfried

Jalilzadeh, Shapour

Illig, Thomas

Gieger, Christian

Guo, Chao-Yu

Larson, Martin G.

Wichmann, H. Erich

Marban, Eduardo

O'Donnell, Christopher J.

Hirschhorn, Joel N.

Kaeaeb, Stefan

Spooner, Peter M.

Meitinger, Thomas

Chakravarti, Aravinda ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany

[4] GSF, Natl Res Ctr Environm & Hlth, Inst Human Genet, D-85764 Neuherberg, Germany

[5] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA

[6] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[7] Harvard Univ, Broad Inst, Cambridge, MA 02139 USA

[8] MIT, Cambridge, MA 02139 USA

[9] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[10] GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany

[11] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[12] Univ Munich, Inst Informat Management Biometry & Epidemiol, D-81377 Munich, Germany

[13] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[14] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[15] Childrens Hosp, Program Genom, Boston, MA 02115 USA

[16] Univ Munich, Dept Med 1, D-81377 Munich, Germany

[17] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2006年 / 38卷 / 06期

关键词：

D O I：

10.1038/ng1790

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP ( CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation.

引用

页码：644 / 651

页数：8

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