常见的肝脂酶基因促进体变异决定了对强化降脂治疗的临床反应
A Zambon1, S S Deeb, B G Brown
1Department of Medicine, University of Washington, Seattle, WA 98195-6426, USA. brunzell@u.washington.edu
Circulation
|February 15, 2001
概括
具有肝脂酶 (HL) 基因CC基因型的个体在降脂疗法期间表现出最显著的冠状动脉疾病 (CAD) 回归,这表明对治疗反应有很强的遗传影响.
科学领域:
- 遗传学和分子生物学
- 心血管医学 心血管医学
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 肝脂酶 (HL) 基因促进体中的-514C->T多态性影响HL活性,LDL颗粒密度和HDL2胆固醇水平.
- 具有CC基因型的个体通常表现出更高的HL活性,导致更多的异位性LDL颗粒.
- 众所周知,强化降脂疗法可降低HL活性并改善脂蛋白概况,可能促进冠状动脉疾病 (CAD) 的回归.
研究的目的:
- 调查具有CC基因型的个体,其特征是具有更有异位性脂质特征,是否经历强化CAD回归,以响应密集的降脂疗法.
- 为了确定HL基因中的-514C->T多态是否作为接受降脂治疗的患者临床结果的预测因素.
主要方法:
- 定量血管造影用于评估49名中年男性的冠状动脉狭窄的变化,这些男性患有脱脂症和经过密集降脂治疗的已确立的CAD.
- 使用聚合酶连锁反应放大分析了肝脂酶 (HL) 基因多态性.
- 使用 (14) C标记基质测量HL活性,并通过密度梯度超离心确定LDL (低密度脂蛋白) 颗粒浮力.
主要成果:
- 在不同的HL促进体基因型中观察到对降脂疗法的显著反应差异.
- 具有CC基因型的受试者表现出HL活性降低幅度最大 (P<0.005),LDL密度 (P<0.005) 和HDL(2) -C (P<0.05) 改善幅度最大.
- 血管图分析显示,96%的CC基因型受试者经历了CAD回归,而TC的60%和没有TT基因型受试者 (P<0.001).
结论:
- 在HL基因中的-514C->T多态性是冠状动脉狭窄症变化的显著预测因中年男性患有CAD和失脂症的血脂降低治疗的反应.
- 这些发现表明,HL介导的对LDL代谢的影响有助于观察到的临床益处.
- 这种遗传多态性强烈地影响了脂质和临床对降脂药物的反应.
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