低密度脂蛋白降低胆固醇的遗传变异与2型糖尿病风险之间的关联:元分析
Luca A Lotta1, Stephen J Sharp1, Stephen Burgess2
1MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
JAMA
|October 5, 2016
概括
在NPC1L1附近降低低密度脂蛋白胆固醇 (LDL- C) 的基因变异与2型糖尿病的风险增加有关. 这一发现表明LDL-C降低疗法的潜在不良代谢作用.
科学领域:
- 遗传学
- 代谢疾病
- 药物基因组学
背景情况:
- 在NPC1L1和HMGCR附近的低密度脂蛋白胆固醇 (LDL- C) 降低基因为ezetimibe和他类药物的疗效提供了替代作用.
- HMGCR等位基因与2型糖尿病风险增加有关,这与他类药物试验的观察结果相一致.
- NPC1L1等位基因与2型糖尿病风险之间的关联仍未确立.
研究的目的:
- 研究NPC1L1中的或附近的LDL降低基因与其他基因之间的关联.
- 检查与这些遗传变异相关的2型糖尿病风险.
- 探索降脂疗法的潜在代谢不良影响.
主要方法:
- 进行了基因关联研究的分析.
- 包括2型糖尿病,冠状动脉疾病和对照患者.
- 在1991年至2016年期间从欧洲和美国人口中收集数据.
主要成果:
- 降低NPC1L1的LDL-C变体与冠状动脉疾病有反向关联,但与2型糖尿病有直接关联.
- 对于PCSK9变体,每次LDL- C降低也会增加2型糖尿病的风险.
- 虽然通过遗传变异降低LDL-C同样降低了冠状动脉疾病的风险,但2型糖尿病的相关性是异质的,基因特异的.
结论:
- 暴露于降低LDL-C的基因变异,特别是NPC1L1附近,与2型糖尿病的风险增加有关.
- 这些发现提供了LDL-C降低疗法的潜在不良代谢后果.
- 基因特异性关联凸显了与遗传降脂变异相关的代谢风险的复杂性.
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