胶原蛋白VI家族蛋白在支气管扩张症诊断与治疗中的应用价值:一项孟德尔随机化研究  

The Application Value of Collagen VI Family Proteins in the Diagnosis and Treatment of Bronchiectasis:A Mendelian Randomization Study

作　　者：郭琴琴 成孟瑜 苏林 GUO Qinqin;CHENG Mengyu;SU Lin(Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan,Shanxi 030032,P.R.China)

机构地区：[1]山西白求恩医院(山西医学科学院同济山西医院)山西医科大学第三医院,太原030032

出　　处：《中国呼吸与危重监护杂志》2025年第2期115-123,共9页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：2022年度山西省高等学校科技创新项目(2022L160)。

摘　　要：目的使用孟德尔随机化(Mendelian randomization,MR)探索胶原蛋白VI(Collagen VI,COL6)家族蛋白COL6A1、A2、A3与支气管扩张症之间是否存在因果关系。方法使用MR联合基于汇总数据的孟德尔随机化分析方法(summary-data-based Mendelian randomization,SMR)进行主要分析,其中COL6家族蛋白作为暴露数据,支气管扩张症作为结局数据,提取了顺式蛋白数量性状位点数据(cis-pqtl)用于分析,将结果进行了meta汇总,随后使用英国生物银行血浆蛋白组研究项目来源的COL6A3-cis-pqtl数据进行进一步验证,并使用共定位分析进一步探索了COL6蛋白与支扩之间的关联性。结果MR及SMR结果发现COL6A3与支扩存在负相关因果关系(p-MRmeta=0.005,OR=0.30,p-SMRmeta=0.004,OR=0.26),验证阶段同样发现COL6A3与支扩存在负相关因果关系(p-MRmeta=0.000007,OR=0.27,p-SMRmeta=0.0003,OR=0.29),共定位支持COL6A3与支气管扩张之间存在共同因果变异(rs972974),PP.H4=0.967/0.876。结论COL6A3与支气管扩张症之间存在负相关因果关系,低表达的COL6A3会导致支气管扩张症发病风险增加,COL6A3是支气管扩张症潜在的生物标志物及药物治疗开发靶点。Objective To explore the causal relationship between the Collagen VI(COL6)family proteins COL6A1,A2,and A3 and bronchiectasis using the Mendelian randomization(MR)method.Methods The primary analysis was conducted using MR combined with summary-data-based Mendelian randomization(SMR)analysis.COL6 family proteins were used as exposure data,and bronchiectasis was used as outcome data.Cis-protein quantitative trait locus(cis-pQTL)data were extracted for analysis,and the results were meta-analyzed.Subsequently,COL6A3-cis-pQTL data from the UK Biobank plasma proteome study were used for further validation.Colocalization analysis was also performed to further explore the association between COL6 proteins and bronchiectasis.Results MR and SMR results revealed a negative causal relationship between COL6A3 and bronchiectasis(p-MRmeta=0.005,OR=0.30;p-SMRmeta=0.004,OR=0.26).The validation phase also confirmed the negative causal relationship between COL6A3 and bronchiectasis(p-MRmeta=0.000007,OR=0.27;p-SMRmeta=0.0003,OR=0.29).Colocalization analysis supported the presence of a shared causal variant(rs972974)between COL6A3 and bronchiectasis(PP.H4=0.967/0.876).Conclusion There is an inverse causal relationship between COL6A3 and bronchiectasis.Low expression of COL6A3 increases the risk of developing bronchiectasis,making COL6A3 a potential biomarker and therapeutic target for drug development in bronchiectasis.

关 键 词：胶原蛋白VI COL6A3 支气管扩张症 孟德尔随机化 共定位分析 

分 类 号：R562.22[医药卫生—呼吸系统]