对低密度脂蛋白胆固醇和发生2型糖尿病的遗传倾向
Akshaya Ravi1,2,3,4, Satoshi Koyama1,2,3,4, So Mi Jemma Cho1,2,3,4
1Program of Medical and Population Genetics, Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, Cambridge, Massachusetts.
JAMA cardiology
|January 15, 2025
概括
影响低密度脂蛋白胆固醇 (LDL-C) 的遗传因素与2型糖尿病 (T2D) 风险有相反的关系. 降低LDL-C基因与增加T2D风险有关,突出显示胆固醇和糖尿病之间的复杂相互作用.
科学领域:
- 心血管遗传学 心血管遗传学
- 代谢性疾病流行病学
背景情况:
- 降低低密度脂蛋白胆固醇 (LDL-C) 会降低冠状动脉疾病 (CAD) 的风险,但可能会增加2型糖尿病 (T2D) 的风险.
- 胆固醇水平与T2D风险之间的关联的遗传基础尚未完全理解.
研究的目的:
- 调查LDL-C升高的遗传倾向与发生T2D的风险之间的关联.
- 探索影响LDL-C水平的遗传变异如何影响T2D和CAD风险.
主要方法:
- 一项基于人口的前性队列研究,使用英国生物库的数据,包括全外因子测序和基因造型.
- 参与者根据家族性高胆固醇血症 (FH),APOB或PCSK9中的预测功能丧失 (pLOF) 变体,以及LDL-C多基因风险评分 (PRS) 五分位数进行分类.
- 考克斯的比例危险回归模型被用来评估遗传性LDL-C因子与T2D/CAD事件之间的关联,并对相关共变量进行调整.
主要成果:
- 在361,082名参与者中,对降低LDL-C的遗传倾向 (例如,FH,pLOF变体) 与T2D风险有不同的关联.
- 在pLOF组观察到的T2D风险最高 (HR,1.48),而FH组的风险较低 (HR,0.65).
- 在LDL-C PRS和T2D风险之间发现了反向关联;非常高的LDL-C PRS与较低的T2D风险相关 (HR,0.72),而非常低的LDL-C PRS与更高的风险相关 (HR,1.26). 随着较高的LDL-C PRS,CAD风险增加.
结论:
- 影响LDL-C水平的遗传因素与T2D风险有相反的关联,这表明存在复杂的遗传相互作用.
- 与基因决定的较低的LDL-C相关的T2D风险增加背后的机制需要进一步研究.
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