Mediating Role of Blood Metabolites in the Relationship Between Immune Cell Traits and Heart Failure: A Mendelian Randomization and Mediation Analysis

被引:0
作者
Liu, Yi [1 ]
Shen, Chenfu [2 ,3 ]
Cao, Yu [1 ]
机构
[1] Sichuan Univ, West China Hosp, West China Sch Med, Dept Emergency Med,Lab Emergency Med, Chengdu, Peoples R China
[2] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China
[3] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2025年 / 14卷 / 06期
基金
中国国家自然科学基金;
关键词
blood metabolites; HF; immune cell; mediation analysis; Mendelian randomization; GENETIC-VARIANTS; DENDRITIC CELL; OXIDATION; STRESS;
D O I
10.1161/JAHA.124.037265
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Observational studies have shown a significant association between immune cells and heart failure (HF). Nevertheless, the precise biological mechanisms underlying this association remain unclear. Methods: To investigate the causative relationships and underlying mechanisms between immune cell traits and adult HF, 3 main methods of Mendelian randomization were used: 2-sample Mendelian randomization, multivariable Mendelian randomization with controlling for several factors affecting HF, and mediation analysis. Results from the inverse variance-weighted model indicated that genetic predispositions for human leukocyte antigen-type DR (HLA DR) on CD33dim HLA DR+ CD11b+ (odds ratio, 0.967 [95% CI, 0.939-0.996]; P=0.028) may be associated with a reduced risk of HF. Although the association between HF and HLA DR on CD33 dim HLA DR+ CD11b+ did not withstand multiple-testing correction, the Mendelian randomization results (P-IVW <0.05) decrease the likelihood that the observational results are due to chance. Results: Our 2-step mediation analysis demonstrated that genetic predispositions for HLA DR on CD33dim HLA DR+ CD11b+ (odds ratio,1.085 [95% CI, 1.020-1.155]; P=0.010) was associated with increased levels of the metabolite Octadecanedioate, while genetic predispositions for Octadecanedioate levels (odds ratio, 0.917 [95% CI, 0.849-0.991]; P=0.028) was associated with a reduced risk of HF. Moreover, our results also demonstrated that the association between HLA DR on CD33dim HLA DR+ CD11b+ and HF was possibly mediated by Octadecanedioate levels, with a mediation proportion of 21.4% [95% CI, 43.7 -0.998]. Conclusions: These findings underscore the importance of HLA DR on CD33dim HLA DR+ CD11b+ in the development of HF, with Octadecanedioate levels acting as a possible mediator in this pathway.
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页数:12
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