摘要
目的通过两样本孟德尔随机化(MR)方法分析循环炎症蛋白与肝硬化风险的因果关系。方法采用全基因组关联研究(GWAS)中与91种血浆炎性蛋白强相关的单核苷酸多态性(SNP)作为工具变量,肝硬化作为结局变量,采用随机效应逆方差加权法(IVW)、MR Egger回归、优势比(OR)及其95%置信区间用以评估因果关系,同时采用MR-多效性残差和离群值(MR-PRESSO)和Q检验进行敏感性分析。结果7种特异性循环炎性蛋白的表达与肝硬化之间的因果关系通过IVW方法得到证实。结果显示,白血病抑制因子[OR(CI)=0.66,P=9.73×10^(-5)]、白细胞介素-18[OR(CI)=0.76,P=0.013]、肿瘤坏死因子配体超家族成员12[OR(CI)=0.75,P=0.024]、单核细胞趋化蛋白-2[OR(CI)=0.89,P=0.036]、C-C基序趋化因子25[OR(CI)=0.84,P=0.039]等5种血浆炎症蛋白与肝硬化呈负相关,是肝硬化的保护因素,T细胞表面糖蛋白CD5[OR(CI)=1.29,P=0.035]、C-X-C基序趋化因子10[OR(CI)=1.32,P=0.043]与肝硬化呈正相关,是肝硬化的危险因素。MR-PRESSO、Q检验、MR Egger截距测试以及留一法的结果均显示了结果的稳定性。结论基于遗传数据的研究结果显示,白血病抑制因子、白细胞介素-18、肿瘤坏死因子配体超家族成员12、单核细胞趋化蛋白-2、C-C基序趋化因子25的水平升高是肝硬化发病中的保护因素,而T细胞表面糖蛋白CD5、C-X-C基序趋化因子10水平的升高是肝硬化发病的危险因素。
Objective To analyze the causal relationship between circulating inflammatory proteins and the risk of liver cirrhosis by the two-sample Mendelian randomization(MR)method.Methods Single nucleotide polymorphisms(SNP)strongly associated with 91 plasma inflammatory proteins in genome-wide association studies(GWAS)were used as instrumental variables,and liver cirrhosis was used as the outcome variable.Random-effects inverse variance-weighted(IVW),MR Egger regression,odds ratio(OR)and its 95%confidence interval were used to evaluate the causal relationship.Simultaneously,sensitivity analysis was performed using MR pleiotropy residuals and outliers(MR-PRESSO)and the Q-test.Results The causal relationship between the expression of seven specific circulating inflammatory proteins and liver cirrhosis was confirmed by the inverse variance-weighted(IVW)method.The results showed that five plasma inflammatory proteins,including leukemia inhibitory factor[OR(CI)=0.66,P=9.73×10^(-5)],interleukin-18[OR(CI)=0.76,P=0.013],tumor necrosis factor ligand superfamily member 12[OR(CI)=0.75,P=0.024],monocyte chemoattractant protein 2[OR(CI)=0.89,P=0.036],and C-C motif chemokine 25[OR(CI)=0.84,P=0.039],were negatively correlated with cirrhosis and were protective factors for cirrhosis.T cell surface glycoprotein CD5[OR(CI)=1.29,P=0.035]and C-X-C motif chemokine 10[OR(CI)=1.32,P=0.043]were positively correlated with cirrhosis and were risk factors for cirrhosis.The results of the MR-PRESSO,Q-test,MR-Egger intercept test,and leave-one-out method all showed the stability.Conclusion The research results indicated that the increased levels of leukemia inhibitory factor,interleukin-18,tumor necrosis factor ligand superfamily member 12,monocyte chemoattractant protein-2,and C-C motif chemokine 25 were protective factors in the development of cirrhosis,while the increased levels of T cell surface glycoprotein CD5 and C-X-C motif chemokine 10 were risk factors for the development of cirrhosis based on genetic data.
作者
李茂
周施君
强丽
陈敏
唐彧
吴刚
Li Mao;Zhou Shijun;Qiang Li;Chen Min;Tang Yu;Wu Gang(Department of Infectious Diseases,Hospital of Southwest Medical University,Luzhou 646000,China)
出处
《中华肝脏病杂志》
北大核心
2025年第6期577-586,共10页
Chinese Journal of Hepatology
基金
泸州-西南医大联合基金(2021LZXNYD-J16)。
关键词
肝硬化
诊断
循环炎症蛋白
孟德尔随机化
全基因组关联研究
Liver cirrhosis
Diagnosis
Plasma inflammatory protein
Mendelian randomization
Genome-wide association studies
作者简介
通信作者:吴刚,Email:wugang2020@swmu.edu.cn。
