白细胞计数与静脉血栓栓塞的关联:双向孟德尔随机化研究  

Association of white blood cell count with venous thromboembolism:a two-way Mendelian randomization study

作　　者：郭展立 王媛 张磊 李嘉媛 李若柠 冬颖[2] 孙建军[2] GUO Zhanli;WANG Yuan;ZHANG Lei;LI Jiayuan;LI Ruoning;DONG Ying;SUN Jianjun(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010059,Inner Mongolia,China;Department of Pharmacy,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010059,Inner Mongolia,China)

机构地区：[1]内蒙古医科大学药学院,内蒙古呼和浩特010059 [2]内蒙古医科大学附属医院药学部,内蒙古呼和浩特010059

出　　处：《中国临床药理学与治疗学》2025年第4期446-455,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金地区项目(81960770);内蒙古自治区卫生健康科技计划项目(202202184);内蒙古自治区“草原英才”工程青年创新人才(一层次)支持项目(Q2022084);内蒙古医科大学重点项目(YKD2023ZD002);内蒙古医科大学“致远”人才项目(ZY20242133);内蒙古自治区高等学校科学研究项目(NJZY22623)。

摘　　要：目的:探讨中性粒细胞、单核细胞、嗜酸性细胞、嗜碱性细胞、淋巴细胞5种白细胞计数与静脉血栓栓塞(VTE)之间的因果关联。方法:利用孟德尔随机化(MR)分析方法,以5种白细胞相关的遗传变异基因作为工具变量,以VTE发生风险作为结局变量,采用逆方差加权法(IVW)为主要分析方法,MR-Egger回归法、加权中位数(WME)、简单模型及加权模式法作为补充,对5种白细胞计数与VTE之间的因果关联进行分析,再进行反向MR分析。结果:中性粒细胞和淋巴细胞计数对VTE发生风险具有因果关联,其中中性粒细胞计数IVW(OR=0.867,95%CI:0.761-0.981,P=0.031),MREgger(OR=0.754,95%CI:0.571-0.996,P=0.048),加权中位数法(OR=0.846,95%CI:0.729-0.981,P=0.027),加权模型(OR=0.748,95%CI:0.595-0.942,P=0.014);淋巴细胞计数IVW(OR=0.838,95%CI:0.741-0.949,P=0.005),加权中位数法(OR=0.024,95%CI:0.718-0.977,P=0.024)。反向MR分析表明VTE发生风险对中性粒细胞计数有因果关联,其中IVW(OR=0.989,95%CI:0.980-0.999,P=0.024)。结论:中性粒细胞与淋巴细胞计数对VTE发生风险有因果关联,中性粒细胞与淋巴细胞数量降低可能会增加VTE的发生风险;VTE发生风险对中性粒细胞计数有因果关联,VTE发生风险降低可能会增加中性粒细胞数量。需进一步研究来了解这种因果关系背后的潜在生物学机制。AIM:To explore the causal association between the counts of five types of white blood cells-neutrophils,monocytes,eosinophils,basophils,and lymphocytes-and venous thromboembolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic variants associated with the five types of white blood cells as instrumental variables,and venous thromboembolism occurrence risk as the outcome variable,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),simple model,and weighted mode methods used as supplements,to analyze the causal association between the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RESULTS:Neutrophil and lymphocyte counts are causally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median estimate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lymphocyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median estimate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neutrophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occurrence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to understand the underlying biological mechanisms behind this relationship.

关 键 词：静脉血栓栓塞 血栓栓塞疾病 白细胞计数 孟德尔随机化 

分 类 号：R965.2[医药卫生—药理学]