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Association between regulatory T cells and ischemic heart disease: a Mendelian randomization study
Yucheng Hou1, Ke Si1, Jingyue Yang1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
Journal of Thoracic Disease
|February 27, 2024
Summary
Elevated CD28 on regulatory T cells (Tregs) may protect against ischemic heart disease (IHD). This Mendelian randomization study suggests targeting CD28 on Tregs could be a novel therapeutic strategy for IHD prevention.
Area of Science:
- Immunology
- Cardiovascular Disease Genetics
- Genetic Epidemiology
Background:
- Immune response imbalance contributes to coronary atherosclerosis and ischemic heart disease (IHD).
- Regulatory T cells (Tregs) are crucial in atherosclerotic plaque development; Treg dysfunction accelerates disease progression.
- Observational studies have limitations in clarifying the causal link between peripheral Treg variations and IHD risk.
Purpose of the Study:
- To investigate the potential causal relationship between regulatory T cell (Treg) biomarkers and the risk of ischemic heart disease (IHD) using Mendelian randomization.
- To determine if genetic variations associated with Treg subtypes causally influence IHD susceptibility.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) summary data.
- Instrumental variables (IVs) were derived from 51 Treg subtypes (3,757 individuals) and tested for association with IHD (30,952 cases, 187,845 controls).
- Bidirectional MR analysis was conducted, with statistical significance assessed after false-discovery rate (FDR) correction.
Main Results:
- 197 single-nucleotide polymorphisms (SNPs) were identified as IVs for 51 Treg subtypes.
- Four Treg subtypes showed a significant protective causal effect against IHD risk, notably those with CD28 expression on CD4+ Tregs.
- Reverse MR analysis did not reveal significant causal associations after FDR correction.
Conclusions:
- Elevated CD28 expression on CD4+ regulatory T cells (Tregs) is identified as a potential protective factor against ischemic heart disease (IHD).
- Targeting CD28 expression on Tregs presents a promising novel therapeutic avenue for managing and preventing IHD.
