91种循环炎症蛋白与呼吸道感染之间的因果关系:一项双向孟德尔随机化研究  

Causality between 91 circulating inflammatory proteins and respiratory infections:a bidirectional Mendelian randomization study

作　　者：张来 张秀英[2] 张诗瑶 魏晨浩 李兆洋 ZHANG Lai;ZHANG Xiuying;ZHANG Shiyao;WEI Chenhao;LI Zhaoyang(Liaoning University of Traditional Chinese Medicine,First Clinical College Shenyang,Shenyang,Liaoning 116600,P.R.China;Department of Pediatrics,First Affiliated Hospital of Liaoning University of Chinese Medicine,Shenyang,Liaoning 110000,P.R.China)

机构地区：[1]辽宁中医药大学第一临床学院,辽宁沈阳116600 [2]辽宁中医药大学第一附属医院儿科,辽宁沈阳110000

出　　处：《中国呼吸与危重监护杂志》2024年第12期864-875,共12页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家自然科学基金(8197152087)

摘　　要：目的通过双向孟德尔随机化的方法探讨91种循环炎症蛋白和呼吸道感染之间的因果关系。方法91种炎症循环蛋白的单核苷酸多态性(single nucleotide polymorphism,SNP)来自Olink Target平台上共计14824名欧洲血统受试者的全基因组关联研究GWAS数据,急性支气管炎、急性毛细支气管炎和急性喉炎和气管炎的SNP均来自FinnGen数据库的GWAS汇总数据。以逆方差加权法作为主要研究方法进行双向孟德尔随机化分析,采用Cochran’IVW Q检验法、MR-Egger回归法及逐个剔除法进行敏感性检验以评估异质性及水平多效性。为减少Ⅰ类错误发生率提高研究可行性进行Bonferroni校正。结果C-X-C基序趋化因子6(chemokine C-X-C motif ligand 6,CXCL6)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)、肝细胞生长因子(hepatocyte growth factor,HGF)、白细胞介素10(interleukin-10,IL-10)、C-X3-C基序趋化因子配体1(CX3CL1)、肿瘤坏死因子相关激活诱导因子(TNF-related activation-induced cytokine,TRANCE)水平与急性支气管炎存在因果关系,其中MMP-1水平[OR:1.239,95%CI:1.1106-1.3822,P<0.0005]与急性支气管炎存在显著因果关系且起到促进作用。巨噬细胞炎症蛋白-1α水平(macrophage inflammatory protein-1α,MIP-1α)、信号传导的淋巴细胞激活分子水平、FMS样酪氨酸激酶3配体(Fms-related tyrosine kinase 3 ligand,FIt3L)水平与急性毛细支气管炎存在潜在因果关系。C-X-C基序趋化因子5(CXCL5)水平、T细胞表面糖蛋白CD6亚型(CD6)水平、成纤维细胞生长因子-19(fibroblast growth factor 19,FGF-19)水平、C-C基序趋化因子配体23(CCL23)水平、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)水平、肿瘤坏死因子配体超家族成员12(TNFSF12)水平与急性喉炎和气管炎存在潜在因果关系。反向孟德尔随机化分析中,急性支气管炎、急性毛细支气管炎与91种炎症因子水平无阳性结果。急性喉炎和气管炎[Objective To investigate the causal relationship between 91 circulating inflammatory proteins and respiratory tract infection by bidirectional Mendelian randomization.Methods single nucleotide polymorphisms(SNPs)for 91 inflammatory circulating proteins were derived from GWAS data from a genome-wide association study of 14824 subjects of European ancestry on the Olink Target platform,and SNPs for acute bronchitis,acute bronchiolitis,and acute laryngitis and tracheitis were derived from GWAS pooled data in the FinnGen database.Inverse variance weighting method was used as the main research method to conduct bidirectional Mendelian randomization analysis,and Cochran’IVW Q test,MR-Egger regression method and one by one elimination method were used to conduct sensitivity tests to evaluate heterogeneity and horizontal pleiotropy.In order to reduce the incidence of Class I errors and improve the feasibility of the study,Bonferroni correction was performed.Results Levels of C hemokine C-X-C motif ligand 6(CXCL6),matrix metalloproteinase-1(MMP-1),hepatocyte growth factor(HGF),interleukin-10(IL-10),chemokine C-X3-C motif ligand 1(CX3CL1),and TNF-related activation-induced cytokine(TRANCE)were causally associated with acute bronchitis.MMP-1 level[OR:1.2390,95%CI:1.1116-1.3822,P<0.0005]had a significant causal relationship with acute bronchitiss and played a promoting role.Levels of macrophage inflammatory protein-1α(MIP-1α),signaling lymphocyte activating molecules,and FMS-associated tyrosine kinase 3 ligand(FIt3L)were potentially causally associated with acute bronchiolitis.There was a potential causal relationship between C-X-C motif chemokine 5(CXCL5),T cell surface glycoprotein CD6 subtype(CD6),fibroblast growth factor 19(FGF-19),C-C motif chemokine 23(CCL23),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor ligand superfamily member 12(TNFSF12)levels and acute laryngitis and tracheitis.In reverse Mendelian randomization analysis,there were no positive results between acute bronchitis,acute bronchiolit

关 键 词：呼吸道感染 孟德尔随机化 炎症蛋白 急性喉炎和气管炎 急性支气管炎 急性毛细支气管炎 

分 类 号：R562.21[医药卫生—呼吸系统]