Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis

doi:10.3389/fcvm.2023.1217922

科研成果详情

题名	Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis
作者	Lou, Chen 1; Meng, Zhizhen 2; Shi, Yi-Yi 3; Zheng, Rui 4; Qian, Song-Zan5; Pan, Jingye5
发表日期	2023-08-07
发表期刊	Frontiers in cardiovascular medicine 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Mendelian randomization (MR) analysis genetic association lipid lipid-lowering drugs sepsis
其他关键词	PARTICLE-SIZE ; ATHEROSCLEROSIS ; ATORVASTATIN ; THERAPY ; STATINS ; TRIAL
摘要	The impact of lipid-lowering medications on sepsis is still not well defined. A Mendelian randomization (MR) study was carried out to probe the causal connections between genetically determined lipids, lipid-reducing drugs, and the risk of sepsis., Data on total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and triglycerides (TG) were retrieved from the MR-Base platform and the Global Lipids Genetics Consortium in 2021 (GLGC2021). Our study categorized sepsis into two groups: total sepsis and 28-day mortality of sepsis patients (sepsis28). The inverse-variance weighted (IVW) method was the primary method used in MR analysis. Cochran's Q test and the MR-Egger intercept method were used to assess the heterogeneity and pleiotropy., {AbstractText=In the MR analysis, we found that ApoA-I played a suggestively positive role in protecting against both total sepsis (OR, 0.863 per SD increase in ApoA-I; 95% CI, 0.780-0.955; P = 0.004) and sepsis28 (OR, 0.759; 95% CI, 0.598-0.963; P = 0.023). HDL-C levels were also found to suggestively reduce the incidence of total sepsis (OR, 0.891 per SD increase in HDL-C; 95% CI, 0.802-0.990; P = 0.031). Reverse-MR showed that sepsis28 led to a decrease in HDL-C level and an increase in TG level. In drug-target MR, we found that HMGCR inhibitors positively protected against total sepsis (1OR, 0.719 per SD reduction in LDL-C; 95% CI, 0.540-0.958; P = 0.024). LDL-C and HDL-C proxied CETP inhibitors were found to have a protective effect on total sepsis, with only LDL-C proxied CETP inhibitors showing a suggestively protective effect on sepsis28. In Mediated-MR, BMI exhibited a negative indirect effect in HMGCR inhibitors curing sepsis. The indirect impact of ApoA-I explained over 50% of the curative effects of CETP inhibitors in sepsis.}, Our MR study suggested that ApoA-I and HDL-C protected against sepsis, while HMGCR and CETP inhibitors showed therapeutic potential beyond lipid-lowering effects. ApoA-I explained the effects of CETP inhibitors. Our study illuminates how lipids affect sepsis patients and the effectiveness of new drugs, opening new avenues for sepsis treatment.
资助项目	Research Incubation Project of the First Affiliated Hospital of Wenzhou Medical University [FHY2019048]; Foundation of Wenzhou City Science amp; Technology Bureau [Y20210713]; Wenzhou High-level Innovation Team for Critical Care and Intelligent Treatment [88923001]
出版者	FRONTIERS MEDIA SA
ISSN	2297-055X
卷号	10
DOI	10.3389/fcvm.2023.1217922
页数	10
WOS类目	Cardiac & Cardiovascular Systems
WOS研究方向	Cardiovascular System & Cardiology
WOS记录号	WOS:001051924800001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	37621565
SCOPUSEID	2-s2.0-85168501330
通讯作者地址	[Qian, Song-Zan]Department of Intensive Care Unit,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China ; [Pan, Jingye]Department of Intensive Care Unit,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Cardiology and Cardiovascular Medicine
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182494
专题	第一临床医学院（信息与工程学院）、附属第一医院附属第一医院附属第一医院_重症医学科（ICU）
通讯作者	Qian, Song-Zan; Pan, Jingye
作者单位	1.School of The First Clinical Medical Sciences,Wenzhou Medical University,Wenzhou,China; 2.Department of Emergency,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Yiwu,China; 3.Department of Anesthesiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 4.Department of Critical Care Medicine,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Zhejiang,Hangzhou,China; 5.Department of Intensive Care Unit,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	温州医科大学
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Lou, Chen,Meng, Zhizhen,Shi, Yi-Yi,et al. Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis[J]. Frontiers in cardiovascular medicine,2023,10.
APA	Lou, Chen, Meng, Zhizhen, Shi, Yi-Yi, Zheng, Rui, Qian, Song-Zan, & Pan, Jingye. (2023). Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis. Frontiers in cardiovascular medicine, 10.
MLA	Lou, Chen,et al."Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis".Frontiers in cardiovascular medicine 10(2023).