循环炎症因子与感音神经性聋之间的因果关系:一项双样本孟德尔随机化研究  

Causal relationship between circulating inflammatory factors and sensorineural hearing loss:A two-way Mendelian randomization study

作　　者：邱招凤 常玮[1] 郭建宙 刘宇 赵亚会 QIU Zhaofeng;CHANG Wei;GUO Jianzhou;LIU Yu;ZHAO Yahui(Department of Otolaryngology,Heping Hospital affiliated to Changzhi Medicine College,Changzhi,Shanxi,046000,China)

机构地区：[1]长治医学院附属和平医院耳鼻咽喉科,山西长治046000

出　　处：《中国耳鼻咽喉头颈外科》2024年第11期717-721,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：2020年长治医学院附属和平医院院级项目(HPYJ2020141)。

摘　　要：目的通过孟德尔随机化方法探讨循环细胞因子与感音神经性聋(sensorineural hearing loss,SNHL)的因果关系。方法基于英国生物样本库的大规模全基因组关联研究(GWAS)数据集用于识别与暴露和结果相关的单核苷酸多态性(SNP)。选择与暴露数据显著相关(P<5e-6)并与F统计量中的暴露密切相关的SNP(F>10)作为工具变量进行双样本孟德尔随机化分析。使用MR-Egger回归和逆方差加权评估其因果影响。进行敏感性分析以评估结果的稳健性。结果血管内皮生长因子(VEGF)(OR=1.04,95%CI:1.01-1.07,P=0.00),基质细胞衍生因子1α(SDF-1α)(OR=1.10,95%CI:1.02-1.18,P=0.01)以及白细胞介素13(IL-13)(OR=1.04,95%CI:1.01-1.06,P=0.01)、IL-10(OR=1.06,95%CI:1.02-1.11,P=0.01)、IL-7(OR=1.05,95%CI:1.01-1.08,P=0.00)升高增加SNHL的风险。逆向分析并未发现SNHL显著影响这些细胞因子的水平。在工具变量中没有观察到明显的异质性或水平多效性。结论VEGF、SDF-1α、IL13、IL10和IL7水平升高与SNHL有正相关性,为进一步进行生物标志物用于SNHL的预测、治疗和预防提供新的靶点。OBJECTIVE To explore the causal relationship of circulating cytokines and sensorineural deafness by Mendelian randomization.METHODS Large-scale genome-wide association studies(GWAS)data sets based on UK Biobank were used to identify single nucleotide polymorphisms(SNP)associated with exposure and outcome.The SNP(F>10)significantly associated with exposure data(P<5e-6)and strongly associated with exposure in the F statistic was selected as the instrumental variable for a two-sample Mendelian randomization analysis.The causal effect was estimated using MREgger,regression and inverse variance weighting(IVW).Sensitivity analysis was performed to assess the robustness of the results.RESULTS This study confirmed that VEGF(OR=1.04,95%CI:1.01-1.07,P=0.00),SDF-1α(OR=1.10,95%CI:1.02-1.18,P=0.01)and IL-13(OR=1.04,95%CI:1.01-1.06,P=0.01),IL-10(OR=1.06,95%CI:1.02-1.11,P=0.01),IL-7(OR=1.05,95%CI:1.01-1.08,P=0.00)increased the risk of sensorineural deafness.The backward analysis did not find that sensorineural deafness significantly affected the levels of these cytokines.No significant heterogeneity or horizontal pleiotropy was observed among the instrumental variables.CONCLUSION This study reveals a positive correlation between elevated levels of VEGF,SDF-1α,IL-13,IL-10,and IL-7 with sensorineural hearing loss,providing novel targets for further development of biomarkers for the prediction,treatment,and prevention of sensorineural hearing loss.

关 键 词：耳聋 细胞因子类 遗传异质性 孟德尔随机化 感应神经性聋 炎症因子 多效性 

分 类 号：R764.431[医药卫生—耳鼻咽喉科]