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心血管风险蛋白质的遗传结构
Mark D Benson1,2, Qiong Yang3, Debby Ngo2,4
1Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (M.D.B.).
Circulation
|December 21, 2017
概括
这项研究确定了影响血蛋白水平与心血管疾病风险的新遗传因素. 这些发现为脂蛋白生物学和心血管疾病病理生理学提供了新的见解.
科学领域:
- 遗传学和基因组学
- 蛋白质组学
- 心血管疾病研究
背景情况:
- 发现了156种与心血管疾病风险相关的人体血蛋白.
- 该研究旨在发现这些与风险相关的蛋白质的遗传决定因素.
研究的目的:
- 确定与156种心血管疾病风险相关蛋白质的血水平相关的遗传变异.
- 探索心血管疾病病理生理学的新生物学途径.
- 通过实验验证一种与阿波利波蛋白E水平的新遗传关联.
主要方法:
- 在两个基于人群的队列中进行了全基因组关联研究 (GWAS) 和外基因组阵列分析 (弗雷明汉心脏研究后代和马尔默饮食和癌症研究).
- 用线性混合效应模型评估遗传变异与血蛋白水平之间的关联.
- 一个细胞模型系统被用来实验验证一种新的遗传关联.
主要成果:
- 来自GWAS的120个和来自外体阵列分析的41个位蛋白关联被确定,许多之前未被描述.
- 这些遗传基因解释了多达66%的血蛋白变异,远远超过常见的临床因素.
- 通过实验验证实了阿波利波蛋白E水平与转录因子酸酶1G之间的新相关性,显示酸酶1G倒置降低了阿波利波蛋白E转录和水平.
结论:
- 发现了几十种与心血管疾病风险相关的蛋白质的新遗传决定因素.
- 实验证实了酸酶1G在脂蛋白生物学中的新作用.
- 作为心血管疾病研究的资源,提供了每个蛋白质的全基因组和外基因组数组数据.
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