A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization
A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization
复制标题
DOI：
10.1038/ng1790
复制
发表时间：
2006-06-01
期刊：
影响因子：
30.8
通讯作者：
Chakravarti, Aravinda
中科院分区：
文献类型：
--
作者：
Arking, Dan E.;Pfeufer, Arne;Chakravarti, Aravinda
心电图QT间隔的极端是心脏复极化的量度，与心血管死亡率的增加有关。我们通过一项针对该定量性状的常见遗传变异来通过全基因组的关联研究来影响这一定量性状，该研究对200名受试者的200名受试者的QT间隔分布在德国的Kora队列中的3,966名受试者的极端分布，并在德国进行了3,966名受试者，并对选定标记的随访筛选队列的其余部分。我们验证了来自德国2,646名受试者的两个独立样本和来自美国弗雷明汉心脏研究的1,805名受试者的统计学意义的发现。这项全基因组研究确定了NOS1AP（CAPON），即神经元一氧化氮合酶的调节剂，是调节心脏复极化的新靶标。大约60％的欧洲血统受试者含有NOS1AP遗传变异的至少一个小等位基因，该等位基因解释了QT间隔变化的1.5％。
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.