血液代谢物与高血压性心脏病的因果关系:两样本双向孟德尔随机化研究  

Causality Relationship Between Blood Metabolites and Hypertensive Heart Disease:A Two-sample Bidirectional Mendelian Randomization Study

作　　者：陈佳永 唐梅玲 卢健棋[2] 庞延 杨尚冰 毛美玲 罗文宽 张艺博 CHEN Jiayong;TANG Meiling;LU Jianqi(Guangxi University of Chinese Medicine,Guangxi 530200,China)

机构地区：[1]广西中医药大学,南宁530200 [2]广西中医药大学第一附属医院心血管内科,南宁530022 [3]广西中医药大学第一附属医院急诊科,南宁530022

出　　处：《医学研究杂志》2024年第12期67-71,共5页Journal of Medical Research

基　　金：国家自然科学基金地区基金资助项目(82160887);国家中医临床研究基地业务建设第二批科研专项(JDZX2015146);国家中医药传承创新中心项目(2023019-10);广西自然科学基金资助项目(2021GXNSFBA196018);广西岐黄学者培养项目(2022015-003-02);广西自然科学基金资助项目(面上项目)(2021GXNSFAA220111);广西南宁市科学研究与技术开发计划项目(20233040);广西中医药管理局自筹经费科研课题(GXZYA20230065);广西高水平中医药重点学科-中医心病学(2024016-02-02)。

摘　　要：目的利用两样本双向孟德尔随机化(Mendelian randomization,MR)分析研究血液代谢产物与高血压性心脏病(hypertensive heart disease,HHD)之间的因果关系。方法从全基因组关联研究(Genome-Wide Association Study,GWAS)数据库中获取HHD数据。一项包含1400种血液代谢产物的GWAS作为暴露因素,选择与暴露因素显著相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量(instrumental variable,IV)。借助R软件(V4.3.2)的“TwoSampleMR”“gwasglue”等对1400种血液代谢产物与HHD之间的因果关系进行分析。采用MR-Eggeer回归法、加权中位数法(weighted median,WM)、逆方差加权法(inverse-varianceweighted,IVW)等方法,并进行异质性、多效性、敏感度等一系列验证分析。最后进行反向MR分析。结果通过IVW分析1400种血清代谢产物与HHD之间的因果关系,结果显示,脱氧胆酸-葡萄糖醛酸(OR=0.847,95%CI:0.770~0.931)是保护因素,随着此代谢物的增加,HHD的发病风险反而降低;丁酸/异丁酸(4∶0)(OR=1.316,95%CI:1.134~1.528)是危险因素,随着代谢物的增加,HHD的发病风险越大。结论丁酸/异丁酸(4∶0)具有促HHD作用,脱氧胆酸-葡萄糖醛酸对HHD具有抑制作用。这可能是未来HHD研究和治疗的新思路、新依据。Objective To evaluate the causal relationship between blood metabolites and hypertensive heart disease(HHD)using two-sample bidirectional Mendelian randomization(MR)analysis.Methods HHD data were obtained from the Genome-wide Association Study(GWAS)database.A GWAS containing 1400 blood metabolites was used as an exposure factor,and single nucleotide polymorphism(SNP)significantly associated with exposure factors were selected as instrumental variable(IV).The causal relationship between 1400 blood metabolites and HHD was analyzed by‘TwoSampleMR’and‘gwasglue’packages of R software(V4.3.2).MR-Eggeer regression method,weighted median(WM)method,and inverse variance weighting(IVW)method and other methods were used.And a series of verification analyses such as heterogeneity,pleiotropic,and sensitivity and so on were performed.Finally,reverse MR analysis was performed.Results IVW analysis of the causal relationship between 1400 blood metabolites and HHD showed that deoxycholic acid glucuronic(OR=0.847,95%CI:0.770-0.931)was a protective factor,and the risk of HHD decreased with the increase of this metabolite.Butyric/isobutyric(4∶0)(OR=1.316,95%CI:1.134-1.528)was a risk factor.With the increase of metabolites,the risk of HHD increased.Conclusion Butyric/isobutyric(4∶0)had effect of promoting HHD,and deoxycholic acid glucuronide had effect of inhibiting HHD.This may be a new idea and new basis for the future research and treatment of HHD.

关 键 词：代谢产物 高血压性心脏病 孟德尔随机化 脱氧胆酸-葡萄糖醛酸 丁酸/异丁酸 

分 类 号：R541[医药卫生—心血管疾病]