低密度脂蛋白胆固醇和肝细胞癌的风险:孟德尔的随机化和调解分析
Jiali Cao1, Ziwen Wang1, Mengpei Zhu1
1Department of Gastroenterology, Liyuan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430077, China.
Lipids in health and disease
|July 31, 2023
概括
这项研究发现,较高的低密度脂蛋白胆固醇 (LDL-C) 水平因果性地降低了肝细胞癌 (HCC) 风险,冠状动脉疾病 (CAD) 起到调解作用. 这些发现为HCC发展和潜在的代谢标提供了新的见解.
科学领域:
- 遗传学和流行病学
- 心血管和代谢疾病 心血管和代谢疾病
- 肝细胞癌研究 肝细胞癌研究
背景情况:
- 以前的研究表明,低密度脂蛋白胆固醇 (LDL-C) 和肝细胞癌 (HCC) 之间存在关联,但由于混因素,因果关系仍然未被证明.
- 这项研究解决了需要澄清LDL-C和HCC之间的因果关系,探索潜在的调解途径.
研究的目的:
- 通过使用孟德尔随机化 (MR) 研究LDL-C对发展HCC的风险的因果作用.
- 为了确定潜在的调解因素,特别是冠状动脉疾病 (CAD),在LDL-C和HCC之间的关系.
- 检查反向因果关系,评估HCC是否影响LDL-C水平.
主要方法:
- 孟德尔随机化 (MR) 分析利用LDL-C,HCC和CAD的全基因组关联研究 (GWAS) 数据.
- 主要分析采用逆方差权衡 (IVW),补充MR-Egger,加权中位数和加权模式方法.
- 使用多变量MR (MVMR) 和调解分析来调整混因素并评估调解效应,使用敏感性分析,包括留出一个测试和异质性/多变性测试.
主要成果:
- 确立了显著的因果关系:较高的LDL-C水平与降低HCC风险相关 (OR=0.703,P=0.034).
- 冠状动脉疾病 (CAD) 在降低HCC风险方面也表现出因果关系 (OR=0.722,P=1.50×10−8) 并被确定为显著的调解者,解释了LDL-C对HCC影响的58.52%.
- MVMR证实了LDL-C和CAD对HCC风险的独立因果作用. 反向MR表明HCC和LDL-C水平之间存在弱负相关性 (OR=0.979,P=0.025).
结论:
- 这项MR研究提供了强有力的证据,证明一种因果关系,即高的LDL-C有利地影响HCC风险,主要通过CAD进行调解.
- 这些发现表明,CAD在将LDL-C与HCC连接的途径中起着至关重要的作用,为HCC病变发生提供了新的视角.
- 这些结果突出了HCC预防和治疗策略的代谢途径内的潜在治疗点.
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