基于孟德尔随机化分析的代谢物与非酒精性脂肪性肝病的因果关系研究  

Study on the causal relationship between metabolites and non-alcoholic fatty liver disease based on Mendelian randomization analysis

作　　者：吴福博 张顺中 牛洪凯 魏勇 WU Fubo;ZHANG Shunzhong;NIU Hongkai;WEI Yong(The Second School of Clinical Medicine of Binzhou Medical University,Yantai 264100,Shandong,China;Department of Hepatobiliary,Pancreatic and Splenic Surgery,Yantai Affiliated Hospital of Binzhou Medical University,Yantai 264100,Shandong,China)

机构地区：[1]滨州医学院第二临床医学院,山东烟台264100 [2]滨州医学院烟台附属医院肝胆胰脾外科,山东烟台2641001

出　　处：《中国现代医生》2025年第12期30-35,共6页China Modern Doctor

摘　　要：目的利用孟德尔随机化分析方法探讨代谢物与非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的因果关系。方法回顾性收集夜莺健康及FinnGen联盟全基因组关联研究数据库汇总统计数据,以逆方差加权为主要分析方法,通过双样本孟德尔随机化方法分析血液循环中的233种代谢物与NAFLD之间的因果关系。结果结果显示糖蛋白乙酰化水平(OR=3.30,95%CI:1.64~6.62,P=0.0008)、大颗粒极低密度脂蛋白(very low-density lipoprotein,VLDL)中游离胆固醇与总脂质的比值(OR=3.50,95%CI:1.63~7.48,P=0.0013)、血清总甘油三酯水平(OR=2.26,95%CI:1.38~3.70,P=0.0012)、饱和脂肪酸水平(OR=2.47,95%CI:1.40~4.36,P=0.0018),VLDL中的总胆固醇水平(OR=2.20,95%CI:1.36~3.59,P=0.0015)、极大颗粒高密度脂蛋白(high-density lipoprotein,HDL)中甘油三酯与总脂质的比值(OR=2.91,95%CI:1.53~5.55,P=0.0011)、极小颗粒VLDL中的甘油三酯(OR=2.27,95%CI:1.43~3.62,P=0.0006)均与NAFLD呈正相关,高密度脂蛋白亚型2中的总胆固醇水平(OR=0.44,95%CI:0.27~0.71,P=0.0007)、HDL中的总胆固醇水平(OR=0.44,95%CI:0.28~0.72,P=0.0009)与NAFLD呈负相关。异质性检验结果表明工具变量之间无显著异质性,分析结果稳健可靠。结论本研究中7种代谢物与NAFLD风险增加有关,2种代谢物与NAFLD风险降低有关,揭示相关代谢物在NAFLD发生和发展中的关键作用。Objective To investigate the causal relationship between circulating metabolites and non-alcoholic fatty liver disease(NAFLD)using Mendelian randomization analysis.Methods Summary statistics from genome-wide association study provided by Nightingale Health and the FinnGen Consortium were retrospectively collected.A two-sample Mendelian randomization analysis was performed to assess the causal effects of 233 blood metabolites on NAFLD,with the inverse-variance weighting method as the primary analytical approach.Results Elevated levels of glycoprotein acetylation(OR=3.30,95%CI:1.64-6.62,P=0.0008),the ratio of free cholesterol to total lipids in very low-density lipoprotein(VLDL)(OR=3.50,95%CI:1.63-7.48,P=0.0013),serum total triglycerides(OR=2.26,95%CI:1.38-3.70,P=0.0012),saturated fatty acids(OR=2.47,95%CI:1.40-4.36,P=0.0018),total cholesterol in VLDL(OR=2.20,95%CI:1.36-3.59,P=0.0015),the ratio of triglycerides to total lipids in very large high-density lipoprote(HDL)(OR=2.91,95%CI:1.53-5.55,P=0.0011),and triglycerides in very small VLDL(OR=2.27,95%CI:1.43-3.62,P=0.0006)were positively associated with NAFLD.Conversely,total cholesterol in high-density lipoprotein 2(OR=0.44,95%CI:0.27-0.71,P=0.0007)and total cholesterol in HDL(OR=0.44,95%CI:0.28-0.72,P=0.0009)were inversely associated with NAFLD.Heterogeneity tests indicated no significant heterogeneity among instrumental variables,confirming the robustness of the findings.Conclusion This study identified seven metabolites associated with an increased risk of NAFLD and two metabolites linked to a reduced risk,highlighting their potential roles in the pathogenesis and progression of NAFLD.

关 键 词：非酒精性脂肪性肝病 孟德尔随机化分析 代谢物 全基因组关联研究 

分 类 号：R657.3[医药卫生—外科学]