Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts
Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts
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DOI：
10.1016/j.ajhg.2012.07.017
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发表时间：
2012-09-07
影响因子：
9.8
通讯作者：
Seidman, Christine
中科院分区：
文献类型：
--
作者：
Bick, Alexander G.;Flannick, Jason;Seidman, Christine
罕见的肌节蛋白变异导致显性肥大和扩张型心肌病。为了评估八个肌节基因的等位基因变异是否与社区中的心脏形态和功能相关，我们对来自心脏研究（FHS）和杰克逊心脏研究（JHS）队列的3,600名个体进行了测序。在总数中，11.2%的人有一个或多个罕见的非同义肌节变异。可能致病的肌节变异的患病率为0.6%，是先前估计的两倍;然而，22例患者中只有4例有肥厚型心肌病的临床表现。在FHS队列中，罕见肌节变异与不良心血管事件风险增加相关（风险比：2.3），表明普通人群的心血管风险评估可从罕见变异分析中获益。
Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis.