Carnitine is causally associated with susceptibility and severity of sepsis: a Mendelian randomization study  

作　　者：Qingju Zhang Xilong Liu Qi Shen Xingfang Wang Jiaojiao Pang Yuguo Chen 

机构地区：[1]Department of Emergency Medicine,Qilu Hospital of Shandong University,Jinan,Shandong,China [2]Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine,Institute of Emergency and Critical Care Medicine of Shandong University,Chest Pain Center,Qilu Hospital of Shandong University,Jinan,Shandong,China [3]Key Laboratory of Emergency and Critical Care Medicine of Shandong Province,Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province,Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine,Shandong Key Laboratory:Magnetic Field-free Medicine and Functional Imaging,Qilu Hospital of Shandong University,Jinan,Shandong,China [4]NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug,Qilu Hospital of Shandong University,Jinan,Shandong,China [5]The Key Laboratory of Cardiovascular Remodeling and Function Research,Chinese Ministry of Education,Chinese Ministry of Health and Chinese Academy of Medical Sciences,The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine,Qilu Hospital of Shandong University,Jinan,Shandong,China

出　　处：《Emergency and Critical Care Medicine》2024年第4期149-154,共6页急危重症医学(英文)

基　　金：This study was supported by the State Key Program of the National Natural Science Foundation of China(82030059);National Natural Science Foundation of China(82172127,81772036,82072144,81671952,81873950,and 81873953);National Key R&D Program of China(2020YFC1512700,2020YFC1512705,2020YFC1512703,and 2020YFC0846600);National S&T Fundamental Resources Investigation Project(2018FY100600,2018FY100602);Taishan Pandeng Scholar Program of Shandong Province(tspd20181220);Taishan Young Scholar Program of Shandong Province(tsqn20161065,tsqn201812129);Youth Top-Talent Project of National Ten Thousand Talents Plan,Qilu Young Scholar Program,and the Fun-damental Research Funds of Shandong University(2018JC011).

摘　　要：Background:Energy metabolism disorders contribute to the development of sepsis.Carnitine is essential for fatty acid metabolism and energy production.Therefore,we aimed to explore whether there is a causal relationship between carnitine levels and sepsis.Methods:Two-sample Mendelian randomization(MR)analysis was performed.The single nucleotide polymorphisms(SNPs)of carnitine from the genome-wide association(GWAS)study were used as exposure instrumental variables,and the susceptibility and severity of sepsis in the UK Biobank were used as outcomes.The inverse-variance weighted(IVW),MR-Egger,and weighted median methods were used to evaluate the causal relationship between exposure and outcomes.Heterogeneity was assessed using IVW and MR-Egger’s and Cochran’s Q tests,and pleiotropy was tested using the MR-Egger intercept and MR-PRESSO.Results:Using the IVW method,a one-standard-deviation increase in genetically determined carnitine levels was found to be associated with increased susceptibility to sepsis in populations under 75 years of age(odds ratio[OR]:2.696;95%confidence interval[CI]:1.127–6.452;P=0.026)and increased severity of sepsis(OR:22.31;95%CI:1.769–281.282;P=0.016).Sensitivity analysis did not re-veal heterogeneity or horizontal pleiotropy;therefore,the results indicated robustness.Conclusion:Genetic susceptibility to increased carnitine levels in the blood may increase the susceptibility and severity of sepsis.There-fore,interventions at an early stage in patients with high carnitine levels may reduce the risk of developing sepsis.

关 键 词：CARNITINE CAUSALITY Genome-wide association study(GWAS) Mendelian randomization SEPSIS 

分 类 号：R73[医药卫生—肿瘤]