Xu Yinyin, Yang Jing, Xue Rong, Zhang Guojiang, Zhang Yanhua
Department of Cardiology, Third People's Hospital of Datong, Datong, Shanxi Province, China.
The First Clinical Medical College of Changzhi Medical College, Changzhi, Shanxi Province, China.
Medicine (Baltimore). 2025 Sep 12;104(37):e43682. doi: 10.1097/MD.0000000000043682.
Myocardial infarction (MI) is a major cause of death worldwide. It is been suspected for a long time that MI is linked to immune cells. However, observational studies are plagued by confounding factors and reverse causality, whether the immune response is a cause or consequence of MI remains unknown. The present study aimed to determine whether genetically immune cells might have a causal effect on MI. According to publicly available genetic data, we assessed the causal relationship between 731 immune cell signatures (7 groups) and MI based on a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms from a genome-wide association study comprising 3757 Sardinians on immune cells were used as exposure instruments. Another summary-level genome-wide association study statistics of MI were used as the outcome data. We primarily used inverse variance weighted, MR-egger, and simple median methods to perform MR analyses. Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. Twenty-seven of 731 immune cell phenotypes are causally associated with MI (odds ratio: 0.94-1.06, 95% confidence interval: 0.80-1.15, P < .048). Among them, 14 immunophenotypes were negatively associated with the occurrence of MI, in other words, the more these immune cell phenotypes, the lower the probability of MI. The remaining 13 immunophenotypes were positively correlated with MI. Our study has demonstrated the close connection between immune cells and MI by genetic means, and revealed the direct causal relationship between these immune cells and MI with the help of MR experiments, which to a certain extent avoids the wastage of manpower, resources, and finance that would be incurred by opening up a large-scale clinical trial to obtain unsatisfactory results. On the other hand, these immune cells shown in our results may become new biomarkers of MI or even potential drug targets for the treatment of MI, thus providing a new target for prevention, diagnosis, and treatment of MI.
心肌梗死（MI）是全球主要的死亡原因。长期以来人们一直怀疑MI与免疫细胞有关。然而，观察性研究受到混杂因素和反向因果关系的困扰，免疫反应是MI的原因还是结果仍然未知。本研究旨在确定基因免疫细胞是否可能对MI产生因果效应。根据公开可用的基因数据，我们基于两样本孟德尔随机化（MR）分析评估了731种免疫细胞特征（7组）与MI之间的因果关系。来自一项包含3757名撒丁岛人的全基因组关联研究中关于免疫细胞的单核苷酸多态性被用作暴露工具。另一项MI的汇总水平全基因组关联研究统计数据被用作结果数据。我们主要使用逆方差加权、MR-egger和简单中位数方法进行MR分析。综合敏感性分析用于验证结果的稳健性、异质性和水平多效性。731种免疫细胞表型中有27种与MI存在因果关联（优势比：0.94 - 1.06，95%置信区间：0.80 - 1.15，P < 0.048）。其中，14种免疫表型与MI的发生呈负相关，也就是说，这些免疫细胞表型越多，MI的发生概率越低。其余13种免疫表型与MI呈正相关。我们的研究通过基因手段证明了免疫细胞与MI之间的紧密联系，并借助MR实验揭示了这些免疫细胞与MI之间的直接因果关系，这在一定程度上避免了开展大规模临床试验却得到不理想结果所造成的人力、资源和财力的浪费。另一方面，我们结果中显示的这些免疫细胞可能成为MI的新生物标志物，甚至成为治疗MI的潜在药物靶点，从而为MI的预防、诊断和治疗提供新的靶点。
