血HDL胆固醇和心肌梗塞的风险:一个门德尔的随机化研究
Benjamin F Voight1, Gina M Peloso, Marju Orho-Melander
1Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA.
Lancet (London, England)
|May 22, 2012
概括
高密度脂蛋白 (HDL) 胆固醇与降低心脏病发作风险有关,但这项研究表明,提高HDL的一些遗传方法不会降低心肌梗塞风险. 这挑战了更高的HDL总是意味着心脏病发作风险更低的想法.
科学领域:
- 心血管遗传学 心血管遗传学
- 生物标志物因果关系
- 心肌梗塞风险因素 心肌梗塞风险因素
背景情况:
- 高血HDL胆固醇与心肌梗塞风险降低有关.
- 高密度胆固醇和心肌梗塞之间的因果关系尚不清楚.
- 门德尔随机化是一种强大的方法来评估生物标记因果关系,独立于混因素.
研究的目的:
- 通过使用孟德尔随机化来研究血HDL胆固醇对心肌梗塞风险的因果关系.
- 测试影响HDL胆固醇水平的遗传变异是否因果降低心肌梗塞风险.
主要方法:
- 进行了两个门德尔随机化分析.
- 分析1:使用LIPG基因 (LIPG Asn396Ser) 中的单核酸多态 (SNP) 作为一个仪器.
- 分析2:利用了14个常见的SNP的遗传分数,这些SNP与HDL胆固醇完全相关. 用LDL胆固醇的遗传分数作为阳性对照.
主要成果:
- LIPG396Ser等位基因增加了HDL胆固醇,但与心肌梗塞风险没有关联 (OR 0.99,95% CI 0.88-1.11).
- 对高密度胆固醇的遗传评分没有显示与心肌梗塞风险降低的相关性 (OR 0.93,95% CI 0.68-1.26).
- 对LDL胆固醇的遗传评分显示,与心肌梗塞风险有一致的关联 (OR 2.13,95% CI 1.69-2.69).
结论:
- 某些将血HDL胆固醇升高的遗传机制似乎没有降低心肌梗塞风险.
- 这些发现挑战了假设增加血HDL胆固醇均转化为减少心肌梗塞风险的假设.
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