孟德尔随机化解析AZGP1在心力衰竭中的保护作用
Deciphering the protective role of AZGP1 in heart failure through Mendelian randomization
摘要
Abstract
Objective·To investigate the causal relationship between plasma zinc-alpha-2-glycoprotein 1(AZGP1)and heart failure(HF)by using Mendelian randomization(MR)analysis and experimental validation.Methods·A two-sample MR analysis was performed to assess the causal relationship between AZGP1 and HF by integrating large-scale genome-wide association study(GWAS)data on plasma proteins and HF.The inverse-variance weighted(IVW)method was employed as the primary analytical approach,supplemented by MR-Egger regression,weighted median,and simple median methods.Horizontal pleiotropy was tested by using MR-PRESSO global test and MR-Egger intercept analysis.Colocalization analysis was conducted to validate genetic locus overlap.Additionally,a clinical cohort(84 HF patients and 68 healthy controls)was analyzed,with plasma AZGP1 levels quantified by enzyme-linked immunosorbent assay(ELISA).Results·MR analysis showed that elevated plasma AZGP1 levels were significantly associated with reduced HF risk(OR=0.82,95%CI 0.75‒0.90,P=1.70×10-5).Colocalization analysis confirmed that AZGP1 expression and HF shared causal genetic variants(posterior probability for H4=0.69).Sensitivity and reverse MR analyses supported the robustness of the results.ELISA confirmed that plasma AZGP1 levels were significantly lower in HF patients compared to healthy controls,reinforcing its protective role in HF.Conclusion·This study demonstrates AZGP1 exerts a protective causal effect on HF and may serve as a potential biomarker for HF treatment.关键词
心力衰竭/AZGP1/血浆蛋白/孟德尔随机化/生物标志物Key words
heart failure/AZGP1/plasma protein/Mendelian randomization/biomarker分类
医药卫生引用本文复制引用
李龙,赵霞,金珊,李泽莹,吕福强,庞丽娟,刘克坚..孟德尔随机化解析AZGP1在心力衰竭中的保护作用[J].上海交通大学学报（医学版）,2025,45(8):1035-1045,11.基金项目
国家自然科学基金(82060054) （82060054）
新疆生产建设兵团科技计划项目(2023AB018-12) （2023AB018-12）
湛江市科技发展专项资金(2023A214) （2023A214）
湛江市疾病防治重点项目专题(2022A01103) （2022A01103）
湛江中心人民医院高层次人才科研启动经费项目(2022A15,2022A16) （2022A15,2022A16）
2024人才发展基金-天山英才医药卫生中青年骨干人才(CZ001216) （CZ001216）
石河子大学博士基金项目(BS202205). National Natural Science Foundation of China(82060054) （BS202205）
Science and Technology Program of Xinjiang Production and Construction Corps(2023AB018-12) （2023AB018-12）
Zhanjiang Municipal Science and Technology Development Special Funds(2023A214) （2023A214）
Zhanjiang Municipal Key Project for Disease Prevention and Control(2022A01103) （2022A01103）
Scientific Research Startup Funding Project for High-Level Talents at Central People's Hospital of Zhanjiang(2022A15,2022A16) （2022A15,2022A16）
2024 Talent Development Fund-Tianshan Talent Program for Young and Middle-aged Medical Backbones(CZ001216) （CZ001216）
Doctoral Research Foundation of Shihezi University(BS202205). （BS202205）
