Bicuspid aortic valve is heritable
Bicuspid aortic valve is heritable
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DOI：
10.1016/j.jacc.2004.03.050
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发表时间：
2004-07-07
影响因子：
24
通讯作者：
Benson, DW
中科院分区：
文献类型：
--
作者：
Cripe, L;Andelfinger, G;Benson, DW
先前的研究已经建立了二叶式主动脉瓣（BAV）的家族聚集性，可能表明遗传。我们的目的是统计检验BAV的分离模式是否与遗传一致，并估计遗传效应（遗传力）的大小。背景二叶式主动脉瓣发生在1%的人群中，使其成为最常见的心血管畸形（CVM）。二叶式主动脉瓣通常是主动脉瓣狭窄或关闭不全的先兆，并且通常与其他CVM相关，包括主动脉根部扩张。这些研究结果的遗传和发育的意义仍然hubbled.METHODS先证者与BAV，我们获得了三代家族史和超声心动图的一级亲属。BAV和BAV和/或其他CVM的遗传度（h（2））使用基于最大似然的方差分解进行估计，该方差分解扩展到计算机软件包Sequential Oligogenic Linkage Analysis（SOLAR，圣安东尼奥，Texas）中实现的二分性状。在74例患者中发现了二叶式主动脉瓣（患病率= 24%）。共有97名患者患有BAV和/或其他CVM（患病率= 31%），包括主动脉缩窄、室间隔缺损或房间隔缺损、二尖瓣异常、主动脉根部扩张或左心发育不良综合征。BAV和BAV和/或其他CVM的遗传力（h2）分别为89%和75%.结论BAV的高遗传力表明在本研究人群中BAV的决定几乎完全是遗传的。BAV和其他心血管异常的遗传性表明，瓣膜畸形可能是原发于瓣膜发育缺陷或继发于心脏发育的其他因素。(C)2004年，美国心脏病学会基金会。
OBJECTIVES Previous studies have established familial clustering of bicuspid aortic valve (BAV), presumably indicating genetic inheritance. Our objective was to statistically test whether the segregation pattern of BAV is consistent with genetic inheritance and to obtain an estimate of the size of the genetic effect (heritability).BACKGROUND Bicuspid aortic valve occurs in 1% of the population, making it the most common cardiovascular malformation (CVM). Bicuspid aortic valve is frequently an antecedent to aortic valve stenosis or insufficiency and is often associated with other CVMs, including aortic root dilation. The genetic and developmental significance of these findings remains obscure.METHODS In 50 probands with BAV, we obtained a three-generation family history and echocardiograms on first-degree relatives. Heritability (h(2)) of BAV and BAV and/or other CVMs were estimated using maximum-likelihood-based variance decomposition extended to dichotomous traits implemented in the computer package Sequential Oligogenic Linkage Analysis Routines (SOLAR, San Antonio, Texas).RESULTS A total of 309 probands and relatives participated. Bicuspid aortic valve was identified in 74 individuals (prevalence = 24%). A total of 97 individuals had BAV and/or other CVM (prevalence = 31%), including aortic coarctation, ventricular or atrial septal defect, abnormal mitral valve, aortic root dilation, or hypoplastic left heart syndrome. The heritability (h 2) of BAV and BAV and/or other CVMs were 89% and 75%, respectively.CONCLUSIONS The high heritability of BAV suggests that in this study population BAV determination is almost entirely genetic. The heritability of BAV plus other cardiovascular anomalies suggests that valve malformation can be primary to defective valvulogenesis or secondary to other elements of cardiogenesis. (C) 2004 by the American College of Cardiology Foundation.