中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (23): 5992-5999.doi: 10.12307/2026.350

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

免疫细胞与心血管疾病风险的关联：欧洲人群全基因组关联研究

黄  哲1，尚宝令2，3，姚耿圳2，3，潘光明2，3   

  1. 1广州中医药大学，广东省广州市   510405；2广东省中医院，广东省广州市   510120；3广州中医药大学第二临床医学院，广东省广州市   510120
  • 收稿日期:2025-06-06 接受日期:2025-08-12 出版日期:2026-08-18 发布日期:2025-12-31
  • 通讯作者: 姚耿圳，博士，副主任医师，广东省中医院，广东省广州市 510120；广州中医药大学第二临床医学院，广东省广州市 510120 通讯作者：潘光明，博士，主任医师，广东省中医院，广东省广州市 510120；广州中医药大学第二临床医学院，广东省广州市 510120
  • 作者简介:黄哲，女，1998年生，广东省潮州市人，汉族，广州中医药大学在读硕士，主要从事儿童心血管疾病的防治工作。
  • 基金资助:
    国家中医药管理局重点研究室建设项目(国中医药科技发[2012]27号-5)，项目参与人：尚宝令；国家中医药管理局第七批全国老中医药专家学术经验继承项目(国中医药办人教函[2022]76号)，项目负责人：姚耿圳；国家中医药管理局中医药人才培养重点学科建设项目“中医心病学”(0102023703)，项目参与人：尚宝令；广东省中医药局项目(20215004)，项目参与人：尚宝令；广州市科技计划项目(2023A03J0230)，项目负责人：姚耿圳；广东省中医院中医学术流派传承工作室建设项目(中医二院[2013]233号)，项目参与人：尚宝令

Association between immune cells and cardiovascular disease risk: a genome-wide association study in European populations

Huang Zhe1, Shang Baoling2, 3, Yao Gengzhen2, 3, Pan Guangming2, 3   

  1. 1Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 2Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, Guangdong Province, China; 3The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
  • Received:2025-06-06 Accepted:2025-08-12 Online:2026-08-18 Published:2025-12-31
  • Contact: Yao Gengzhen, MD, Associated chief physician, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, Guangdong Province, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China Corresponding author: Pan Guangming, MD, PhD, Chief physician, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, Guangdong Province, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, Guangdong Province, China
  • About author:Huang Zhe, MS candidate, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    The Key Research Laboratory Construction Project of National Administration of Traditional Chinese Medicine (Lingnan TCM Academic School Inheritance), No. [2012]27-5 (to SBL [project participant]); Inheriting the Academic Experience of the Seventh Batch of National Veteran TCM Experts of National Administration of Traditional Chinese Medicine, No. [2022]76 (to YGZ); Key Discipline Construction Project for Talent Cultivation of National Administration of Traditional Chinese Medicine, No. 0102023703 (to SBL [project participant]); Project of Traditional Chinese Medicine Bureau of Guangdong Province, No. 20215004 (to SBL [project participant]); Guangzhou Science and Technology Plan Project, No. 2023A03J0230 (to YGZ); Traditional Chinese Medicine Academic School Inheritance Studio Construction Project of Guangdong Provincial Hospital of Chinese Medicine, No. [2013]233 (to SBL [project participant])

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摘要：



文题释义：
免疫细胞亚型：指基于表面标志物和功能特征划分的免疫细胞群体。此次研究分析了731种免疫表型，涵盖T细胞(如CD4+、CD8+)、B细胞(如记忆B细胞)、单核细胞(如CD14+ CD16-)、树突细胞等，这些亚型的量化数据来自欧洲人群全基因组关联研究，每种亚型均通过流式细胞术进行定义。
孟德尔随机化：是一种基于遗传变异的因果推断方法，核心是利用与暴露因素强相关的单核苷酸多态性作为工具变量，通过三大假设(即相关性、独立性、排他性)推断暴露对结局的因果效应。

背景：既往研究提示免疫细胞亚型与心血管疾病风险相关，但由于混杂因素的影响，他们之间的因果关系尚不明确。
目的：评估免疫细胞亚型与心血管疾病之间的潜在因果关系。
方法：研究数据来源主要涉及3个数据库：GWAS Catalog是由美国国家人类基因组研究所和欧洲生物信息学研究所共同维护的数据库，UK biobank是由英国政府及惠康基金会支持的英国人群基因组、健康及疾病表型数据库，IEU OpenGWAS是由英国布里托斯大学MRC流行病学单元开发的以欧洲人群为主的GWAS数据库，均为开放数据库，研究已获得相关机构审查委员会批准。以731个免疫细胞表型作为暴露因素，以7种心血管疾病(心房颤动、扩张型心肌病、冠状动脉粥样硬化性心脏病、心力衰竭、肥厚型心肌病、高血压及瓣膜性心脏病)作为结局因素，进行双样本孟德尔随机化分析，主要使用逆方差加权和加权中位数方法进行孟德尔随机化分析和敏感性分析，评估异质性和多效性。
结果与结论：①经错误发现率校正后，免疫表型对心房颤动和高血压具有统计学显著影响。5种细胞类型与心房颤动风险相关，包括CD11c on monocytes(OR=0.917，95%CI：0.876-0.960)、FSC-A on myeloid dendritic cells(OR=0.942，95%CI：0.910-0.974)、CX3CR1 on CD14+ CD16- monocytes(OR=1.045，95%CI：1.022-1.070)、CX3CR1 on monocytes(OR=1.050，95%CI：1.024-1.076)以及CX3CR1 on CD14+ CD16+ monocytes(OR=1.050，95%CI：1.024-1.077)。筛选出3种对高血压具有保护作用的免疫表型：CD19 on switched memory B cells(OR=0.986，95%CI：0.980-0.993)、CD25++CD8+ T cells(OR=0.993，95%CI：0.990-0.997)和CD25++CD8+ T cells绝对值计数(OR=0.993，95%CI：0.989-0.996)。在敏感性分析中均未观察到潜在的异质性或水平多效性。②研究发现4种单核细胞和1种髓样树突状细胞与心房颤动之间有因果关系，1种记忆B细胞和2种T细胞与高血压之间存在潜在因果关系，提示监测和治疗心房颤动、高血压时考虑免疫细胞表型的必要性。此次研究采用公共数据库进行分析，为中国人群免疫细胞亚群和心血管疾病的相关研究提供了参考，同时为国人进一步防治心房颤动和高血压提供借鉴。

https://orcid.org/0009-0003-3883-369X (黄哲)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 心血管疾病, 免疫, 免疫细胞亚型, 全基因组关联分析(GWAS), 孟德尔随机化, 心房颤动, 高血压

Abstract: BACKGROUND: Previous studies have linked immune cells to cardiovascular disease risk. As confounding factors are incompletely addressed, the causal relationship between them remains unclear.
OBJECTIVE: To evaluate the potential causal relationship between immune cells and cardiovascular disease. 
METHODS: The source of research data mainly involves three databases: Genome-Wide Association Study (GWAS) database (GWAS Catalog, jointly maintained by the National Institute of Human Genomics and the European Institute of Bioinformatics), UK biobank (a database of British population genomics, health and disease phenotype supported by the British government and Wellcome Foundation), and IEU OpenGWAS (a GWAS database developed by the MRC Epidemiology Unit of the University of Britos in the United Kingdom, which mainly focuses on European populations). All of them are open databases. The study has been approved by the institutional review board. It employed a two-sample Mendelian randomization approach with 731 immune cell phenotypes as exposure factors and seven types of cardiovascular diseases (atrial fibrillation, dilated cardiomyopathy, coronary atherosclerotic heart disease, heart failure, hypertrophic cardiomyopathy, hypertension, and valvular heart disease) as outcome factors. The primary methods used for Mendelian randomization analysis and sensitivity analysis were inverse variance weighting and weighted median, aiming to evaluate heterogeneity and pleiotropy.
RESULTS AND CONCLUSION: (1) After false discovery rate correction, immunophenotypes exerted a statistically significant effect on atrial fibrillation and hypertension. Five types of cells were related to atrial fibrillation risk, including CD11c on monocytes [odds ratio (OR)=0.917; 95% confidence interval (CI): 0.876-0.960), FSC-A on myeloid dendritic cells (OR=0.942; 95% CI: 0.910-0.974), CX3CR1 on CD14+ CD16- monocytes (OR=1.045; 95% CI: 1.022-1.070), CX3CR1 on monocytes (OR=1.050; 95% CI: 1.024-1.076), and CX3CR1 on CD14+ CD16+ monocytes (OR=1.050; 95% CI: 1.024-1.077). Three immunophenotypes that exert a protective effect on hypertension were identified: CD19 on switched memory B cells (OR= 0.986, 95% CI: 0.980-0.993), CD25++ CD8+ T cells (OR=0.993; 95% CI: 0.990-0.997) and CD25++ CD8+ T cells (OR=0.993; 95% CI: 0.989-0.996). No underlying heterogeneity or horizontal pleiotropy was observed in the sensitivity analysis. (2) The study found a causal relationship between four types of monocytes and one type of myeloid dendritic cells and atrial fibrillation, and a potential causal relationship between one type of memory B cells and two types of T cells and hypertension, suggesting the necessity of considering immune cell phenotypes in monitoring and treating atrial fibrillation and hypertension. This study, based on public datasets, offers important implications for understanding the relationship between immune cell subtypes and cardiovascular disease in the Chinese population, with particular relevance for atrial fibrillation and hypertension management strategies in China.

Key words: cardiovascular disease, immunity, immune cell subtypes, Genome-Wide Association Study (GWAS), Mendelian randomization, atrial fibrillation, hypertension

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