组织蛋白酶与动脉粥样硬化的两样本孟德尔随机化研究  

Causal relationship between proteases and atherosclerosis:a Mendelian randomization study

作　　者：李京谕 赵国安 杨红玲[1] 任雪松[1] 赵琦[1] LI Jingyu;ZHAO Guoan;YANG Hongling;REN Xuesong;ZHAO Qi(Department of Acupuncture,the First Afiliated Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Traditional Chinese Medicine Acupuncture,Tianjin 300000,China)

机构地区：[1]天津中医药大学第一附属医院/国家中医针灸临床医学研究中心针灸科,天津300000

出　　处：《中国分子心脏病学杂志》2025年第1期6587-6593,共7页Molecular Cardiology of China

摘　　要：目的 采用两样本孟德尔随机化(MR)分析方法,探讨组织蛋白酶与动脉粥样硬化(AS)之间潜在的因果关联。方法 从全基因组关联研究(GWAS)数据中获取组织蛋白酶和AS的遗传变异信息,并将该信息作为工具变量。组织蛋白酶的数据来源于INTERVAL研究,共3 301个样本。2种动脉粥样硬化的GWAS数据来源于芬兰数据库(其中冠状动脉粥样硬化394 668个样本,脑动脉粥样硬化412 181个样本)。采用逆方差加权法(IVW)作为主要分析方法,辅以加权中位数、加权模型、简单模型及MR Egger方法。并采用Cochran Q、留一法及MR PRESSO方法进行敏感性及多效性的分析。结果 IVW结果表明,组织蛋白酶B与脑动脉粥样硬化之间存在负向因果关系[优势比(OR)=1.313,95%置信区间(95%CI):1.024~1.685,P=0.032],而未发现其他组织蛋白酶与2种AS之间有因果关系。敏感性分析及多效性分析提示未发现存在异质性及多效性。留一法结果也证明结果的稳健性。结论 组织蛋白酶B与脑动脉粥样硬化之间存在因果关系,并且组织蛋白酶B可能作为一种危险因素增加脑动脉粥样硬化发生、发展的风险。Objective To utilize a two-sample Mendelian randomization(MR) analysis to investigate the potential causal association between proteases and atherosclerosis(AS). By examining the genetic perspective, this research aims to provide references for the etiological factors and prevention of AS. Methods Genetic variation information for cathepsins and AS was obtained from genome-wide association studies(GWAS) and used as instrumental variables. The cathepsin data come from the INTERVAL study, with a total of 3 301 samples. The GWAS data for the two types of AS were derived from the Finngen database(including 394 668 samples for coronary atherosclerosis and 412 181 samples for cerebral atherosclerosis). The main analysis method employed in this study was the inverse variance-weighted method, supplemented by weighted median, weighted mode, simple mode, and MR Egger methods. Sensitivity and pleiotropy analyses were conducted using Cochran′s Q, leave-one-out method, and MR PRESSO method. Results The IVW method revealed a negative causal relationship between protease B and cerebral atherosclerosis(odds ratio [OR]=1.313, 95% confidence interval [95%CI]: 1.024-1.685, P=0.032). No causal relationship was found between other proteases and AS. Sensitivity and pleiotropy analyses indicated no heterogeneity or pleiotropy. The leave-one-out method also confirmed the robustness of the results. Conclusions This study provides evidence of a causal relationship between protease B and cerebral atherosclerosis, suggesting that protease B may serve as a risk factor for the occurrence and development of cerebral atherosclerosis.

关 键 词：组织蛋白酶 动脉粥样硬化 孟德尔随机化分析 

分 类 号：R543.5[医药卫生—心血管疾病]