人免疫细胞表型与瘢痕疙瘩之间因果关系的双样本孟德尔随机化分析  

Two-sample Mendelian randomization analysis of the causal relationship between human immune cell phenotypes and keloids

作　　者：甘文军 王婧薷 何佳 陈晓东 Gan Wenjun;Wang Jingru;He Jia;Chen Xiaodong(First Clinical Medical College,Guangdong Medical University,Zhanjiang 524023,China;Department of Burn,Plastic and Wound Repair Surgery,Foshan First People's Hospital,Foshan 528000,China)

机构地区：[1]广东医科大学第一临床医学院,湛江524023 [2]佛山市第一人民医院烧伤整形创面修复外科,佛山528000

出　　处：《中华烧伤与创面修复杂志》2025年第1期84-93,共10页Chinese Journal of Burns And Wounds

基　　金：国家自然科学基金面上项目(82172205);广东省基础与应用基础研究基金区域联合基金(2020A1515110432);佛山市“十四五”高水平临床重点专科;广东省“十四五”医学临床重点专科。

摘　　要：目的探讨人免疫细胞表型与瘢痕疙瘩之间的因果关系。方法该研究为基于双样本孟德尔随机化(MR)分析的研究。以人免疫细胞表型为暴露因素,以瘢痕疙瘩为结局,从全基因组关联分析数据库中获取免疫细胞表型(3757个样本)与瘢痕疙瘩(668个样本)的数据。将与免疫细胞表型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,应用双样本MR分析评估731种人免疫细胞表型与瘢痕疙瘩之间的因果关系。采用逆方差加权(IVW)法推断因果关系,使用MR-Egger法、加权模式法和加权中位数法进行验证。针对符合假设的免疫细胞表型SNP,利用Cochran Q检验评估异质性,利用MR-Egger回归检验及MR-PRESSO离群值检验评估水平多效性。结果筛选出18204个达到显著阈值(P<1×10^(-5))的SNP作为代表731种免疫细胞表型的工具变量,这些SNP均不是弱工具变量(F值均>10)。根据IVW法,确定了21种与瘢痕疙瘩存在潜在因果关系的免疫细胞表型,其中CD62L-单核细胞绝对计数、初始-成熟B细胞上的CD19表达、IgD^(+)B细胞上的CD19表达、浆细胞前体(浆母细胞)上的CD27表达、CD62L+髓系树突状细胞上的CD86表达、自然杀伤T细胞上的CD45表达、CD39^(+)CD4^(+)调节性T细胞上的CD25表达、来源于单核髓系的抑制细胞上的CD45表达、效应记忆CD8^(+)T细胞上的CD8表达、静息CD4^(+)调节性T细胞上的CD45RA表达与瘢痕疙瘩均呈显著正相关(比值比分别为1.12、1.09、1.08、1.21、1.13、1.12、1.17、1.11、1.10、1.07,95%置信区间分别为1.03~1.23、1.02~1.16、1.01~1.15、1.06~1.38、1.02~1.25、1.01~1.24、1.03~1.33、1.00~1.23、1.00~1.20、1.01~1.13,P<0.05),激活并分泌的CD4^(+)调节性T细胞绝对计数、未转换记忆B细胞上的CD25表达、浆细胞样树突状细胞绝对计数、来源于单核髓系的抑制细胞上的CD14表达、自然杀伤T细胞上的CD8表达、IgD^(+)CD38^(+)B细胞上的CD20表达�Objective To explore the causal relationship between human immune cell phenotypes and keloids.MethodsThis study was based on a two-sample Mendelian randomization(MR)analysis.Human immune cell phenotypes were considered as the exposure factors,and keloid was the outcome.Data on immune cell phenotypes(3757 samples)and keloids(668 samples)were obtained from the genome-wide association study database.Using single nucleotide polymorphisms(SNPs)significantly associated with immune cell phenotypes as instrumental variables with the influence of weak instrumental variables being excluded,two-sample MR analysis was employed to evaluate the causal relationship between 731 human immune cell phenotypes and keloids.The inverse variance weighted(IVW)method was used to infer causal relationships,and the MR-Egger,weighted median,and weighted mode methods were used for validation.For SNPs of immune cell phenotypes meeting the hypothesis,the Cochran Q test was used to assess heterogeneity,and the MR-Egger regression and MR-PRESSO outlier tests were used to evaluate horizontal pleiotropy.ResultsA total of 18204 SNPs meeting the significant threshold(P<1×10^(-5))were selected as instrumental variables for 731 immune cell phenotypes,and none of these SNPs were weak instrumental variables(with F values all>10).According to the IVW method,21 immune cell phenotypes were identified with potential causal relationships to keloids,among which the CD62L-monocyte absolute count,CD19 on naive-mature B cell,CD19 on IgD^(+)B cell,CD27 on plasma blast-plasma cell,CD86 on CD62L+myeloid dendritic cell,CD45 on natural killer T cell,CD25 on CD39^(+)CD4^(+)regulatory T cell,CD45 on monocytic myeloid-derived suppressor cells,CD8 on effector memory CD8^(+)T cell,and CD45RA on resting CD4^(+)regulatory T cell showed significant positive correlations with keloids(with odds ratios of 1.12,1.09,1.08,1.21,1.13,1.12,1.17,1.11,1.10,and 1.07,respectively,95%confidence intervals of 1.03-1.23,1.02-1.16,1.01-1.15,1.06-1.38,1.02-1.25,1.01-1.24,1.03-1.33,1.00-1.23,

关 键 词：瘢痕疙瘩 免疫 细胞 孟德尔随机化分析 免疫系统 数据库 遗传学 因果律 

分 类 号：R622[医药卫生—整形外科]