补体C5/C5a在Graves眼病诊断与治疗中的价值:一项孟德尔随机化研究  

Complement C5/C5a in the diagnosis and treatment of Graves’ophthalmopathy:A Mendelian randomized study

作　　者：朱敏 吴冰萱 陈赵昌辞 陈海燕 熊炜[1] ZHU Min;WU Bingxuan;CHEN-ZHAO Changci;CHEN Haiyan;XIONG Wei(Department of Ophthalmology,Third Xiangya Hospital,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅三医院眼科,长沙410013

出　　处：《中南大学学报(医学版)》2024年第10期1633-1641,共9页Journal of Central South University :Medical Science

基　　金：国家自然科学基金(82071006)。

摘　　要：目的:Graves眼病是一种复杂的器官特异性自身免疫性疾病,发病机制尚不明确。补体系统中的核心成分5/5a(component 5/5a,C5/C5a)可能在该疾病的病理过程中发挥重要作用。本研究旨在利用孟德尔随机化(Mendelian randomization,MR)方法探究C5/C5a与Graves眼病的因果关系,以期为Graves眼病的诊断与治疗提供新的理论依据。方法:基于全基因组关联分析(genome-wide association study,GWAS)的汇总数据,以补体C5/C5a作为暴露因素,Graves眼病作为结局因素,分析补体C5/C5a与Graves眼病的因果关系,利用共定位分析得出假设的后验概率(posterior probability of hypothesis,PPH),进一步验证补体C5与Graves眼病的遗传关联。结果:Wald比率法模型显示补体C5与Graves眼病呈显著正相关(OR=4.109,95%CI 1.990~8.486,P<0.001),逆方差加权法(inverse variance weighted,IVW)模型显示C5a与Graves眼病同样呈正相关(OR=2.901,95%CI 1.225~6.869,P=0.015),共定位分析显示补体C5与Graves眼病在给定的遗传窗口内共享同一个单核苷酸多态性(single nucleotide polymorphism,SNP)rs7036980,PPH4为0.81(>0.80为概率高)。结论:补体C5/C5a的高水平显著增加Graves眼病的发生风险,通过靶向补体C5的抑制剂可以有效降低Graves眼病的发生风险。Objective:Graves’ophthalmopathy is a complex organ-specific autoimmune disease with an unclear pathogenesis.Complement component 5/5a(C5/C5a),a key element of the component system,may play a significant role in the disease’s pathological process.This study aims to investigate the causal relationship between C5/C5a and Graves’ophthalmopathy using Mendelian randomization(MR)to provide new theoretical insights for its diagnosis and treatment.Methods:Utilizing summary data from genome-wide association study(GWAS),C5/C5a was designated as the exposure factor and Graves’ophthalmopathy as the outcome.The causal relationship between C5/C5a and Graves’ophthalmopathy was analyzed,and colocalization analysis was performed to determine the posterior probability of hypothesis(PPH)and verify the genetic association between C5 and Graves’ophthalmopathy.Results:The Wald ratio model showed a significant positive correlation between C5 and Graves’ophthalmopathy(OR=4.109,95%CI 1.990 to 8.486,P<0.001).Similarly,the inverse variance weighted(IVW)model showed a positive correlation between C5a and Graves’ophthalmopathy(OR=2.901,95%CI 1.225 to 6.869,P=0.015).Colocalization analysis showed that C5 and Graves’ophthalmopathy share a single nucleotide polymorphism(SNP),rs7036980,within the specified genetic window,with a PPH4 value of 0.81(a value>0.80 indicates high probability).Conclusion:Elevated levels of C5/C5a significantly increase the risk of developing Graves’ophthalmopathy.Targeting complement C5 with inhibitors may effectively reduce the risk of Graves’ophthalmopathy.

关 键 词：补体C5 补体C5A GRAVES眼病 孟德尔随机化 共定位分析 

分 类 号：R58[医药卫生—内分泌]