在患有高密度脂蛋白胆固醇升高的人体内皮质脂酶遗传变异的鉴定
Andrew S deLemos1, Megan L Wolfe, Christopher J Long
1Department of Medicine, University of Pennsylvania, Philadelphia, USA.
Circulation
|September 11, 2002
概括
在具有高高密度脂蛋白胆固醇 (HDL-C) 个体中发现了内皮脂酶 (EL) 基因的遗传变异. 这些EL基因变异可能会影响HDL-C水平和心血管疾病风险.
科学领域:
- 遗传学 是一个遗传学.
- 心血管疾病研究研究
- 脂质代谢 脂质代谢是什么
背景情况:
- 高密度脂蛋白胆固醇 (HDL-C) 的升高与心血管疾病风险的降低有关.
- 内皮脂酶 (EL) 在调节HDL-C水平方面发挥作用,如小鼠模型所示.
- 遗传因素对HDL-C水平的变化有很大影响.
研究的目的:
- 研究内皮脂酶 (EL) 基因的遗传变异与高密度脂蛋白胆固醇 (HDL-C) 水平升高之间的关联.
- 识别EL基因及其促进区内的新型遗传变异.
主要方法:
- 在20个患有高HDL-C的个体中,对EL基因促进子区域的所有外显子和1.2千基基的测序.
- 使用限制酶分析识别和确认潜在的功能变异.
- 在黑人对照组,白人对照组和具有高HDL-C的白人个体中确定变异的基因定型.
主要成果:
- 在EL基因中发现了17种变异,证实了6种潜在的功能变异.
- 四种变异导致了氨基酸变化 (Gly26Ser,Thr111Ile,Thr298Ser,Asn396Ser) 和两个促进物 (-303A/C,-410C/G).
- Thr111Ile变异在不同群体中很常见,而其他变异在种族群体和HDL-C水平之间显示出不同的频率,其中一些在白人对照中缺席.
结论:
- 在高HDL-C的个体中发现了内皮脂酶 (EL) 基因中的六种新型,潜在的功能变异.
- 在黑人和白人种群之间,以及在对照组和高HDL-C组之间,观察到EL基因变异的等位基因频率的显著差异.
- 这些发现表明,EL的遗传变异在确定高HDL-C水平和潜在的心血管风险方面起着作用.
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