在社区中,内皮氧化合成位的常见遗传变异以及与腕动脉血管扩张功能的关系
Sekar Kathiresan1, Martin G Larson, Ramachandran S Vasan
1Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA, USA.
Circulation
|September 1, 2005
概括
研究了内皮氧化合成酶 (NOS3) 基因中的遗传变异,以确定它们与内皮功能之间的关联. 在考虑了多项测试后,无论是男性还是女性,都没有发现统计学上显著的联系.
科学领域:
- 心血管遗传学 心血管遗传学
- 分子生物学分子生物学
- 人类遗传学 人类遗传学
背景情况:
- 内皮氧化合成酶 (NOS3) 位点的序列变异与内皮功能有关,但这些发现需要复制.
- 内皮功能对心血管健康至关重要,影响其的遗传因素具有重要意义.
研究的目的:
- 研究NOS3位点的共同遗传变异与内皮功能测量之间的关联.
- 在NOS3中识别与内皮功能相关的特定单核酸多态 (SNPs) 和单核酸类型.
主要方法:
- 在NOS3位点的链接不平衡 (LD) 结构的特征是使用参考谱系中的33个常见SNP.
- 捕获常见变异的18个SNP在无关的弗雷明汉心脏研究参与者中被基因型化 (n=1446用于流介导扩张,n=1043用于高血压流速).
- 进行了统计分析,以评估NOS3SNP,单元型和内皮功能指标之间的关联,并对多次测试进行了校正.
主要成果:
- 三个LD块内的11个SNP在NOS3位点捕获了80%以上的常见单元型变异.
- 在男性的八个NOS3SNP和单元型和内皮功能测量之间观察到名义上显著的关联 (P=0.002).
- 在女性中,NOS3变异和内皮功能测量之间没有发现显著的关联. 在对多次测试进行校正后,经验P值超过0.05.
结论:
- 一个简洁的SNP集有效地捕捉了NOS3位点的共同遗传变异.
- 经过多次测试的严格校正后,在NOS3序列变异和两性内皮功能之间没有发现统计学上显著的关联.
- 在男性中观察到的名义关联需要进一步调查,因为在独立队列中产生假设的发现.
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