美托洛尔与2型糖尿病风险的孟德尔随机化研究  

Mendelian Randomization Study of Metoprolol and Risk of Type 2 Diabetes Mellitus

作　　者：谢志鹏 李阳晨 钟诗龙 赖伟华 XIE Zhipeng;LI Yangchen;ZHONG Shilong;LAI Weihua(School of Medicine,South China University of Technology,Guangzhou,Guangdong,China 510006;Guangdong Provincial People′s Hospital·Guangdong Academy of Medical Sciences,Southern Medical University,Guangzhou,Guangdong,China 510080)

机构地区：[1]华南理工大学医学院,广东广州510006 [2]南方医科大学附属广东省人民医院·广东省医学科学院,广东广州510080

出　　处：《中国药业》2025年第1期42-46,共5页China Pharmaceuticals

基　　金：国家自然科学基金[82274016];广东省人民医院院内项目[2023-08]。

摘　　要：目的探讨美托洛尔与2型糖尿病(T2DM)风险间的因果关系及潜在中介蛋白。方法基于已有最大规模的美托洛尔血药浓度的全基因组关联性分析结果选取遗传工具变量,通过逆方差加权法等孟德尔随机化模型分析美托洛尔与T2DM风险间的因果关系及介导该因果关系的潜在中介蛋白,采用异质性检验、水平多效性检验及留一法评估因果关系的稳健性。结果遗传代理的美托洛尔血药浓度的升高与T2DM风险的降低有关[OR=0.982,95%CI(0.971,0.994),P=0.00216],分泌颗粒蛋白Ⅲ在美托洛尔与T2DM风险间的因果关系中起部分中介作用(占7.52%)。敏感性分析结果显示,因果关系稳健,未检测到潜在的异质性和水平多效性(P>0.05)。结论美托洛尔具有潜在通过上调分泌颗粒蛋白Ⅲ的表达而降低T2DM风险的作用。Objective To investigate the causal relationship and potential mediating proteins between metoprolol and the risk of type 2 diabetes mellitus(T2DM).Methods Genetic instrumental variables were selected based on the results of the largest available genome-wide association analysis of blood concentrations of metoprolol.Mendelian randomization models such as inverse variance weighting were used to analyze the causal relationship between metoprolol and the risk of T2DM and the potential mediating proteins that mediated this causal relationship.Heterogeneity test,horizontal multiple validity test,and leave-one-out method were used to assess the robustness of the causality.Results Genetically-mediated increases in metoprolol blood levels were associated with the reduced risk of T2DM[OR=0.982,95%CI(0.971,0.994),P=0.00216],and the secretograninⅢpartially mediated the causal relationship between metoprolol and the risk of T2DM(7.52%).Sensitivity analysis results showed that the causal relationship was robust,with no potential heterogeneity or horizontal pleiotropy detected(P>0.05).Conclusion Metoprolol has the potential to reduce the risk of T2DM by upregulating secretograninⅢexpression.

关 键 词：美托洛尔 2型糖尿病 分泌颗粒蛋白Ⅲ 孟德尔随机化分析 

分 类 号：R95[医药卫生—药学] R972