91种炎症蛋白与5种心血管疾病的因果关系:双向孟德尔随机化研究  

Causal relationship between 91 inflammatory proteins and 5 cardiovascular diseases:a bidirectional Mendelian randomization

作　　者：陈世崧 黄凯[1] 徐泓杰 徐志云[1] 韩林[1] 刘晓红[1] CHEN Shisong;HUANG Kai;XU Hongjie;XU Zhiyun;HAN Lin;LIU Xi aohong(Department of Cardiovascular Surgery,The First Affiliated Hospital of Naval Medical University(Second Military Medical University),Shanghai 200433,China)

机构地区：[1]海军军医大学(第二军医大学)第一附属医院心血管外科,上海200433

出　　处：《海军军医大学学报》2024年第5期558-568,共11页Academic Journal of Naval Medical University

基　　金：国家自然科学基金(82270379,82170376);上海市科学技术委员会科技创新行动计划(22S31904300).

摘　　要：目的采用孟德尔随机化(MR)和反向MR方法评估91种炎症蛋白与5种心血管疾病(主动脉夹层、动脉瘤、冠心病、非风湿性心瓣膜病和风湿性心瓣膜病)之间的因果关系。方法使用来自欧洲人群的全基因组关联研究(GWAS)数据,利用MR方法和反向MR方法对91种炎症蛋白与5种心血管疾病之间的双向因果关系进行评估分析。MR分析方法包括逆方差加权法、加权中位数法、MR-Egger回归、简单模式和加权模式,敏感性分析包括Cochran’s Q检验、MR-Egger截距检验、MR-PRESSO法和留一法。结果共有16种炎症蛋白可能与心血管疾病风险存在相关性,分别为C-C趋化因子配体(CCL)20、CD5、CCL28、白细胞介素20受体α(IL-20RA)、潜在转化生长因子β1前体(LAP-TGF-β1)、胸腺基质淋巴细胞生成集(TSLP)、胱抑素D(CST5)、白血病抑制因子(LIF)、翻译起始因子4E结合蛋白1(EIF4EBP1)、CCL4、白细胞介素22受体α1(IL-22RA1)、IL-10、IL-17C、单核细胞趋化蛋白(MCP)-2/CCL8、神经秩蛋白(NRTN)、MCP-3/CCL7。此外,心血管疾病的进展可能会导致10种炎症蛋白水平的变化,包括CCL11、IL-8、TNF-β、成纤维细胞生长因子(FGF)-19、白细胞介素10受体α(IL-10RA)、FGF-21、白细胞介素10受体β(IL-10RB)、β-神经生长因子(β-NGF)、CD5和MCP-1/CCL2。结论多种炎症蛋白与5种心血管疾病之间存在双向因果关系,进一步研究各种炎症蛋白与上述心血管疾病之间的相关性具有潜在临床价值。Objective To assess the causal relationships between 91 inflammatory proteins and 5 cardiovascular diseases(including aortic dissection,aneurysm,coronary heart disease,non-rheumatic valve disease,and rheumatic valve disease)by Mendelian randomization(MR)and reverse MR.Methods MR and reverse MR analyses were used to assess bidirectional causality between 91 inflammatory proteins and 5 cardiovascular diseases based on Genome-Wide Association Studies(GWAS)data from European populations.MR analysis methods involved inverse variance weighted,weighted median,MR-Egger,simple mode and weighted mode approaches.Sensitivity analysis methods included Cochran’s Q test,MR-Egger intercept test,MR-PRESSO method,and leave-one-out approach.Results A total of 16 inflammatory proteins might be associated with the risk of cardiovascular diseases,including C-C motif chemokine ligand(CCL)20,CD5,CCL28,interleukin 20 receptorα(IL-20RA),latency-associated peptide transforming growth factorβ1(LAP-TGF-β1),thymic stromal lymphopoietin(TSLP),cystatin D(CST5),leukemia inhibitory factor(LIF),eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1),CCL4,interleukin 22 receptorα1(IL-22RA1),interleukin(IL)-10,IL-17C,monocyte chemoattractant protein(MCP)-2/CCL8,neurturin(NRTN),and MCP-3/CCL7.Furthermore,the progression of cardiovascular diseases might potentially lead to changes in the levels of 10 inflammatory proteins,including CCL11,IL-8,tumor necrosis factorβ(TNF-β),fibroblast growth factor(FGF)-19,interleukin 10 receptorα(IL-10RA),FGF-21,interleukin 10 receptorβ(IL-10RB),β-nerve growth factor(β-NGF),CD5,and MCP-1/CCL2.Conclusion The present study highlights the bidirectional causal relationship between an array of inflammatory proteins and the 5 cardiovascular diseases.Further research on the correlation between various inflammatory proteins and the above cardiovascular diseases has potential clinical value.

关 键 词：炎症 炎症蛋白 心血管疾病 孟德尔随机化 全基因组关联研究 

分 类 号：R54[医药卫生—心血管疾病]