Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (23): 5992-5999.doi: 10.12307/2026.350

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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])

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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