组织蛋白酶与胆石症的孟德尔随机化研究  

Mendelian randomization analysis explores the relationship between cathepsin and cholelithiasis

作　　者：刘萍 丁怡[1] 施龙青 傅琪 杨玉娇 Liu Ping;Ding Yi;Shi Longqing;Fu Qi;Yang Yujiao(Department of Geriatrics,the Third Affiliated Hospital of Soochow University,Changzhou 213000,China;Department of Hepatobiliary and Pancreatic Surgery,the Third Affiliated Hospital of Soochow University,Changzhou 213000,China)

机构地区：[1]苏州大学附属第三医院老年医学科,常州213000 [2]苏州大学附属第三医院肝胆胰外科,常州213000

出　　处：《中华肝胆外科杂志》2025年第1期33-37,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：江苏省卫生健康委员会老年健康科研课题面上项目(LKM2023035);国家骨科与运动康复临床医学研究中心创新基金培育项目(2021-NCRC-CXJJ-PY-33)。

摘　　要：目的:采用孟德尔随机化(MR)分析方法,探究9种组织蛋白酶与胆石症的因果关系。方法:分别从全基因组关联研究数据库和芬兰数据库中筛选与9种组织蛋白酶及胆石症密切相关且相互独立的单核苷酸多态性(SNP)位点。选出与暴露因素对应的SNP作为工具变量。采用逆方差加权(IVW)、加权中位数法、MR-Egger法进行双向MR分析。同时,进行多变量MR(MVMR)分析探究胆石症与组织蛋白酶的关系。使用Cochran’s Q检验、MR-PRESSO法及MR-Egger回归检验异质性和多效性,通过留一法进行敏感性分析。 结果:组织蛋白酶B的水平升高会增加胆石症的风险(IVW法: OR=1.054,95% CI:1.025~1.083, P<0.001),反向MR分析结果表明,组织蛋白酶B与胆石症的风险之间缺乏反向因果关系(IVW法: OR=0.998,95% CI:0.920~1.083, P=0.969)。MVMR分析结果显示,组织蛋白酶B水平的升高与胆石症风险的增加密切相关(IVW法: OR=1.038,95% CI:1.003~1.073, P=0.031)。研究结果均不受多效性、异质性的影响,敏感性分析验证了结果的可靠性。 结论:组织蛋白酶B可以作为胆石症的标志物,对胆石症的治疗具有潜在的指导意义。ObjectiveMendelian randomization analysis(MR)was used to investigate the causal association between nine cathepsins and cholelithiasis.MethodsSingle nucleotide polymorphism(SNP)sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database,respectively.SNP corresponding to exposure factors were selected as instrumental variables.Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted(IVW),weighted median and MR-Egger regression.Additionally,multivariable Mendelian randomization(MVMR)was conducted to estimate the direct effect of cathepsins on cholelithiasis.Cochran's Q test,MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy.And the leave-one-out method was performed for the sensitivity analysis.ResultsThe univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis(IVW:OR=1.054,95%CI:1.025-1.083,P<0.001).The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B(IVW:OR=0.998,95%CI:0.920-1.083,P=0.969).A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis(IVW:OR=1.038,95%CI:1.003-1.073,P=0.031).None evidence of significant pleiotropy and heterogeneity was observed,which was verified by sensitivity analysis.ConclusionCathepsin B may serve as a marker for cholelithiasis,and has important guiding significance in cholelithiasis treatment.

关 键 词：孟德尔随机化分析 组织蛋白酶 胆石症 

分 类 号：R65[医药卫生—外科学]