Journal of Shanghai Jiao Tong University (Medical Science) >

2025 , Vol. 45 >Issue 8: 1035 - 1045

DOI: https://doi.org/10.3969/j.issn.1674-8115.2025.08.011

Evidence-based medicine

Deciphering the protective role of AZGP1 in heart failure through Mendelian randomization

  • LI Long ,
  • ZHAO Xia ,
  • JIN Shan ,
  • LI Zeying ,
  • Lü Fuqiang ,
  • PANG Lijuan ,
  • LIU Kejian
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  • 1.National Health Commission Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases (Co-construction by Province and Ministry), The First Affiliated Hospital of Shihezi University, Shihezi 832000, China
    2.Department of Pathology, Central People's Hospital of Zhanjiang, Guangdong Province, Zhanjiang 524000, China
LIU Kejian, E-mail: 25931884@qq.com
PANG Lijuan: E-mail: ocean123456@163.com.

Received date: 2025-03-20

  Accepted date: 2025-05-09

  Online published: 2025-08-20

Supported by

National Natural Science Foundation of China(82060054);Science and Technology Program of Xinjiang Production and Construction Corps(2023AB018-12);Zhanjiang Municipal Science and Technology Development Special Funds(2023A214);Zhanjiang Municipal Key Project for Disease Prevention and Control(2022A01103);Scientific Research Startup Funding Project for High-Level Talents at Central People's Hospital of Zhanjiang(2022A15);2024 Talent Development Fund-Tianshan Talent Program for Young and Middle-aged Medical Backbones(CZ001216);Doctoral Research Foundation of Shihezi University(BS202205)

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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.

Key words： heart failure; AZGP1; plasma protein; Mendelian randomization; biomarker

Cite this article

LI Long , ZHAO Xia , JIN Shan , LI Zeying , Lü Fuqiang , PANG Lijuan , LIU Kejian . Deciphering the protective role of AZGP1 in heart failure through Mendelian randomization[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025 , 45(8) : 1035 -1045 . DOI: 10.3969/j.issn.1674-8115.2025.08.011

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