与CETP抑制剂和他类药物相关的遗传变异与脂蛋白水平和心血管风险的关联
Brian A Ference1,2, John J P Kastelein3, Henry N Ginsberg4
1Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, Michigan.
JAMA
|August 29, 2017
概括
胆固醇转移蛋白 (CETP) 基因变异降低了LDL-C,但心血管风险的降低取决于apoB水平. 结合CETP和HMGCR基因变异显示不一致的脂质变化,影响心血管事件的风险.
科学领域:
- 心血管遗传学和脂质代谢
背景情况:
- 胆固醇转移蛋白 (CETP) 抑制剂降低低密度脂蛋白胆固醇 (LDL- C),但并不总是减少心血管事件.
- 这表明降低LDL- C的方法影响了临床益处,可能与其他脂蛋白变化有关.
研究的目的:
- 调查CETP和3-基-3-甲基-CoA减少酶 (HMGCR) 基因中的遗传变异之间的关联.
- 估计LDL-C,其他脂蛋白 (如apoB) 和心血管事件风险之间的关系.
主要方法:
- 在北美和英国研究中,对超过10万名参与者进行了孟德尔随机分析.
- 对CETP和HMGCR遗传分数,脂质水平和心血管事件风险进行了评估.
- 外部验证使用了多项研究中近19万名参与者的数据.
主要成果:
- 单独CETP变异与较高的HDL- C,较低的LDL- C和apoB相关,并降低了心血管事件的风险.
- 结合CETP和HMGCR变体显示类似的LDL- C降低,但较少的apoB降低,导致减弱的,不显著的风险降低.
- 外部验证证实,与一致的得分相比,具有不一致的LDL- C和apoB变化的遗传得分降低了每LDL- C单位的心血管风险.
结论:
- 对CETP和HMGCR通路的综合遗传影响导致LDL- C和apoB水平发生不一致的变化.
- 与降脂策略相关的心血管风险降低可能比单独的LDL- C更密切地与含有apoB的颗粒的降低有关.
- 降低LDL- C的临床益处可能取决于同时降低的阿波利波蛋白B.
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