Dissecting Causal Relationship Among Immune Cells, Plasma Metabolites and Coronary Atherosclerosis: A Mendelian Randomization Study.

IF 6.2 Q1 IMMUNOLOGY ImmunoTargets and Therapy Pub Date : 2025-03-06 eCollection Date: 2025-01-01 DOI:10.2147/ITT.S508042

Qi Cao, Jiajing Liu, Jingyu Sun, Shuangshuang Qian, Junhuai Song, Haoyang Zheng, Jinkun Wen, Bin Zheng

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Abstract

Background: Circulating immune cells and metabolites are linked to coronary atherosclerosis, but the specific causal relationships and the role of metabolites as mediators remain unclear.

Methods: Summary statistics from GWAS datasets on immune cells (n=3,757), circulating metabolites (n=8,299), and coronary atherosclerosis (cases n=51,589; controls n=343,079) were analyzed using bidirectional Mendelian randomization. Two-step and multivariate Mendelian randomization were employed to identify mediating metabolites, with inverse variance weighting (IVW) as the primary method.

Results: We identified nine immune cell phenotypes, including specific T-cell and monocyte populations, with significant causal links to coronary atherosclerosis. Additionally, 41 plasma metabolites across four metabolic pathways were identified, including 3-hydroxy-2-ethylpropionate and trans-2-hexenoylglycine. Mediation analysis revealed that 3-hydroxy-2-ethylpropionate mediated the effect of IgD+ CD24+ B-cells on coronary atherosclerosis (mediating effect: 0.961; 95% CI: 0.955-0.967), while trans-2-hexenoylglycine regulated IgD+ CD24+ B-cells, showing a mediation ratio of 16.7% (mediating effect: 0.983; 95% CI: 0.981-0.986).

Conclusion: Key immune cell phenotypes and plasma metabolites were linked to coronary atherosclerosis. The roles of 3-hydroxy-2-ethylpropionate and trans-2-hexenoylglycine in regulating B-cell function suggest potential therapeutic targets for prevention and treatment.

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背景：循环免疫细胞和代谢物与冠状动脉粥样硬化有关，但具体的因果关系以及代谢物作为介质的作用仍不清楚：方法：使用双向孟德尔随机法分析了免疫细胞（n=3,757）、循环代谢物（n=8,299）和冠状动脉粥样硬化（病例 n=51,589；对照 n=343,079）的 GWAS 数据集摘要统计。采用双向孟德尔随机法和多变量孟德尔随机法确定中介代谢物，并以反方差加权法（IVW）作为主要方法：结果：我们确定了九种免疫细胞表型，包括特定的 T 细胞和单核细胞群，它们与冠状动脉粥样硬化有着重要的因果关系。此外，我们还发现了四种代谢途径中的 41 种血浆代谢物，包括 3-羟基-2-乙基丙酸酯和反式-2-己烯酰甘氨酸。中介分析显示，3-羟基-2-乙基丙酸酯介导了IgD+ CD24+ B细胞对冠状动脉粥样硬化的影响（中介效应：0.961；95% CI：0.955-0.967），而反式-2-己烯酰甘氨酸调节了IgD+ CD24+ B细胞，中介比率为16.7%（中介效应：0.983；95% CI：0.981-0.986）：结论：关键免疫细胞表型和血浆代谢物与冠状动脉粥样硬化有关。3-羟基-2-乙基丙酸酯和反式-2-己烯酰甘氨酸在调节 B 细胞功能方面的作用为预防和治疗提供了潜在的治疗目标。

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来源期刊

ImmunoTargets and Therapy IMMUNOLOGY-

CiteScore

16.50

自引率

0.00%

发文量

审稿时长

16 weeks

期刊介绍： Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.