人炎症蛋白与瘢痕疙瘩之间因果关系的孟德尔随机化分析  

Mendelian randomization analysis of the causal relationships between human inflammatory proteins and keloids

作　　者：李涛 朱晨晨 陈今源 李璞真 金培生 李雪阳 Li Tao;Zhu Chenchen;Chen Jinyuan;Li Puzhen;Jin Peisheng;Li Xueyang(徐州医科大学附属医院整形外科,徐州221000)

机构地区：[1]徐州医科大学附属医院整形外科,徐州221000

出　　处：《中华烧伤与创面修复杂志》2025年第2期180-187,共8页Chinese Journal of Burns And Wounds

基　　金：国家自然科学基金面上项目(82172224);徐州市卫生健康委科技重点项目(XWKYHT20220136)。

摘　　要：目的 探讨人炎症蛋白与瘢痕疙瘩之间的因果关系.方法 该研究为基于孟德尔随机化(MR)分析的研究.以人炎症蛋白为暴露因素、瘢痕疙瘩为结局,从全基因组关联分析数据库中获取91种炎症蛋白(14 824个样本)与瘢痕疙瘩(668个样本)的数据.设置显著阈值,筛选与炎症蛋白显著相关的单核苷酸多态性(SNP)作为工具变量并排除弱工具变量的影响.针对单个工具变量的分析,采用Wald比率法;针对多个工具变量的分析,采用逆方差加权(IVW)法为主要方法,加权中位数法、简单模式法、加权模式法和MR-Egger法作为补充方法,行双样本MR分析评估炎症蛋白与瘢痕疙瘩之间的因果关系.采用IVW法、加权中位数法和MR-Egger法对前述双样本MR分析中具有统计学意义的炎症蛋白进行多样本MR(MVMR)分析,验证这些炎症蛋白与瘢痕疙瘩之间的独立因果关系.针对符合假设的炎症蛋白的SNP,利用Cochran Q检验评估异质性,采用MR-Egger回归检验和MR-PRESSO离群值检验评估水平多效性,进行留一法分析评估可靠性.结果 筛选出75种炎症蛋白符合暴露因素条件,达到显著阈值的SNP数量从1个到7 082个不等(F值均>10),提示该研究存在弱工具变量偏倚的可能性较小.IVW法分析显示,真核翻译起始因子4E结合蛋白1(4E-BP1)、CD5及骨保护素与瘢痕疙瘩之间均存在显著因果关系(比值比分别为0.50、0.61、0.71,95%置信区间分别为0.32~0.77、0.41~0.89、0.52~0.97,P<0.05);经加权中位数法验证,CD5与瘢痕疙瘩之间存在显著因果关系(比值比为0.61,95%置信区间为0.38~0.97,P<0.05);经简单模式法、加权模式法和MR-Egger法验证,CD5和骨保护素与瘢痕疙瘩之间因果关系均不明显(P>0.05).Wald比率法分析显示,程序性死亡受体配体1(PD-L1)与瘢痕疙瘩之间存在显著因果关系(比值比为1.83,95%置信区间为1.06~3.15,P<0.05).仍需以IVW法结果为准.经IVW法验证,4E-BP1、CD5、骨保护素和ObjectiveTo explore the causal relationships between human inflammatory proteins and keloids.MethodsThis study was based on Mendelian randomization(MR)analysis.Human inflammatory proteins were considered as the exposure factors,and keloid was considered as the outcome.Data on 91 inflammatory proteins(14824 samples)and keloids(668 samples)were obtained from the genome-wide association study database.A significance threshold was established to discern single nucleotide polymorphisms(SNPs)significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded.For the analysis of a single instrumental variable,the Wald ratio method was used;for the analysis of multiple instrumental variables,the inverse variance weighted(IVW)method was used as the primary method,with the weighted median method,simple mode method,weighted mode method,and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids.Using the IVW method,weighted median method,and MR-Egger method to employ multi-sample MR(MVMR)analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis,thus validating their independent causal relationships with keloids.For SNPs of inflammatory proteins conformed to the hypothesis,the Cochran Q test was used to assess heterogeneity,the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy,and the leave-one-out analysis was performed to assess reliability.ResultsSeventy-five inflammatory proteins met the exposure factor criteria,with the number of SNPs reaching a significance threshold ranging from 1 to 7082(with F values all>10),indicating minimal potential for weak instrumental variable bias in this study.The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1(4E-BP1),CD5,and osteopro

关 键 词：瘢痕疙瘩 孟德尔随机化分析 数据库 遗传学 因果律 炎症蛋白 

分 类 号：R73[医药卫生—肿瘤]