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
张来 1张秀英 2张诗瑶 1魏晨浩 1李兆洋1
作者信息
- 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)
- 折叠
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14 824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 growthfactor,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:1.110 6-1.382 2),P＜0.000 5]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[OR:1.0763,95％CI:1.012 9-1.143 7,P=0.017 6]与FGF-19水平存在潜在因果关系.结论 MMP-1水平与急性支气管炎具有显著因果关系,其余CXCL6、HGF、MIP-1α、FIt3L、CXCL5、FGF-19等炎症因子水平与呼吸道感染疾病之间均为潜在因果关系,MMP-1可能为预测或治疗急性支气管炎的重要靶点.
Abstract
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 GW AS data from a genome-wide association study of 14 824 subjects of European ancestry on the Olink Target platform,and SNPs for acute bronchitis,acute bronchiolitis,and acute laryngitis and tracheitis were derived from GW AS 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:1.239 0,95％CI:1.111 6-1.382 2,P＜0.000 5]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 bronchiolitis and 91 inflammatory factors.Acute laryngitis and tracheitis[OR:1.076 3,95％CI:1.012 9-1.143 7,P=0.017 6]were potentially causally associated with FGF-19 levels.Conclusions MMP-1 level have a significant causal relationship with acute bronchitis.The levels of other inflammatory factors such as CXCL6,HGF,MIP-1 alpha,FIt3L,CXCL5,FGF-19 are potentially causally associated with respiratory tract infections.MMP-1 may be an important target for the prediction or treatment of acute bronchitis.
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Key words
Respiratory infection/Mendelian randomization/inflammatory protein/acute laryngitis and bronchitis/acute bronchitis/acute bronchiolitis引用本文复制引用
出版年
2024
NETL
NSTL
万方数据