Yang Xinyu, Yu Yunfeng, Hu Gang, Bai Siyang, Wu Jingyi, Guo Chenlu
Department of Endocrinology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
Medicine (Baltimore). 2025 Jan 31;104(5):e41361. doi: 10.1097/MD.0000000000041361.
The role of circulating immune cells in coronary atherosclerosis remains unclear. This study aimed to assess the causal effects of various immune cells on coronary atherosclerosis using Mendelian randomization (MR). Circulating immune cell datasets were obtained from genome-wide association studies, and coronary atherosclerosis datasets were obtained from FinnGen. Single-nucleotide polymorphisms satisfying the assumptions of association, independence, and exclusivity were screened in the datasets and analyzed using MR, with inverse-variance weighted as the main method. Horizontal pleiotropy, heterogeneity, and sensitivity analyses were performed using the MR-Egger, Cochran Q, and leave-one-out analyses, respectively. The MR analysis showed that effector memory double negative (DN) (cluster of differentiation [CD]4-CD8-) %DN (odds ratio [OR]: 1.042, 95% confidence interval [CI]: 1.008-1.077, P = .014), CD4 on CD39+ CD4+ (OR: 1.027, 95% CI: 1.001-1.054, P = .040), C-X3-C motif chemokine receptor 1 on CD14+ CD16- monocytes (OR: 1.035, 95% CI: 1.010-1.060, P = .006), C-C chemokine receptor 7 on naive CD4+ (OR: 1.035, 95% CI: 1.006-1.076, P = .023), and immunoglobulin D- CD38- %lymphocytes (OR: 1.098, 95% CI: 1.016-1.187, P = .019) were associated with an increased genetic susceptibility to coronary atherosclerosis, with no horizontal pleiotropy (P ≥ .05). Cochran Q showed no heterogeneity (P ≥ .05), and the sensitivity analysis indicated that the results were robust. The MR analysis revealed various markers and immune cell subsets, including effector memory DN (CD4-CD8-) %DN, CD4 on CD39+ CD4+, C-X3-C motif chemokine receptor on CD14+ CD16- monocytes, C-C chemokine receptor 7 on naive CD4+, and IgD- CD38- %lymphocytes, associated with increased genetic susceptibility to coronary atherosclerosis. This provides a genetic explanation for the role of specific immune cells in inducing and exacerbating coronary artery disease and offers new ideas for the exploration of immune markers and immune-targeted drugs.
循环免疫细胞在冠状动脉粥样硬化中的作用仍不清楚。本研究旨在利用孟德尔随机化（MR）评估各种免疫细胞对冠状动脉粥样硬化的因果效应。循环免疫细胞数据集来自全基因组关联研究，冠状动脉粥样硬化数据集来自芬兰基因研究（FinnGen）。在数据集中筛选出满足关联性、独立性和排他性假设的单核苷酸多态性，并使用MR进行分析，以逆方差加权法作为主要方法。分别使用MR-Egger、Cochran Q和留一法分析进行水平多效性、异质性和敏感性分析。MR分析显示，效应记忆双阴性（DN）（分化簇[CD]4-CD8-）%DN（优势比[OR]：1.042，95%置信区间[CI]：1.008-1.077，P = 0.014）、CD39+ CD4+上的CD4（OR：1.027，95%CI：1.001-1.054，P = 0.040）、CD14+ CD16-单核细胞上的C-X3-C基序趋化因子受体1（OR：1.035，95%CI：1.010-1.060，P = 0.006）、幼稚CD4+上的C-C趋化因子受体7（OR：1.035，95%CI：1.006-1.076，P = 0.023）以及免疫球蛋白D-CD38-%淋巴细胞（OR：1.098，95%CI：1.016-1.187，P = 0.019）与冠状动脉粥样硬化遗传易感性增加相关，且无水平多效性（P≥0.05）。Cochran Q显示无异质性（P≥0.05），敏感性分析表明结果稳健。MR分析揭示了各种标志物和免疫细胞亚群，包括效应记忆DN（CD4-CD8-）%DN、CD39+ CD4+上的CD4、CD14+ CD16-单核细胞上的C-X3-C基序趋化因子受体、幼稚CD4+上的C-C趋化因子受体7以及IgD-CD38-%淋巴细胞，它们与冠状动脉粥样硬化遗传易感性增加相关。这为特定免疫细胞在诱导和加重冠状动脉疾病中的作用提供了遗传学解释，并为探索免疫标志物和免疫靶向药物提供了新思路。
