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Causal Relationship Between Immune Cells/Cytokines and Dilated Cardiomyopathy
Bin Qi1, Nan Huang1, Zhi-Jie Yang1
1Department of Cardiology, First Affiliated Hospital, Guangxi Medical University.
Insights
This study investigated the link between immune cells and dilated cardiomyopathy (DCM). Findings suggest certain immune cell levels, like lymphocytes, may protect against DCM, while others, such as basophils and eosinophils, increase risk.
Area of Science:
- Immunology
- Cardiology
- Genetics
Background:
- The causal relationship between immune cell levels and dilated cardiomyopathy (DCM) remains unclear.
- Understanding this link is crucial for developing new therapeutic strategies for DCM.
Purpose of the Study:
- To investigate the potential causal relationship between the levels of various immune cells and cytokines and the risk of DCM.
- To utilize a robust genetic approach to explore these associations.
Main Methods:
- Two-sample Mendelian randomization (TSMR) analysis was performed using genome-wide association study (GWAS) data.
- Single nucleotide polymorphisms (SNPs) associated with immune cell/cytokine levels and DCM were identified.
- Multiple statistical methods including Inverse Variance Weighted (IVW) and MR-Egger regression were employed for causal inference and sensitivity analysis.
Main Results:
- The study identified 1816 SNPs related to host immune status and DCM.
- Elevated lymphocyte levels were found to be protective against DCM (OR=0.91, P=0.005).
- Increased levels of basophils, eosinophils, eosinophil-basophil counts, and C-reactive protein (CRP) were associated with a higher risk of DCM.
Conclusions:
- The findings suggest a potential causal link between specific immune cell profiles and the development of DCM.
- Immune cell status, including lymphocytes, basophils, eosinophils, and CRP levels, may play a significant role in DCM onset.
- Further validation in animal models and clinical trials is warranted to confirm these genetic associations.
Abstract:
To date, whether there is any causal relationship between dilated cardiomyopathy (DCM) and the changes in the levels/expression of immune cells/cytokines is still unclear. This study aimed to investigate the causal relationship between the levels of various types of immune cells/cytokines and DCM. Herein, two-sample Mendelian randomization (MR) (TSMR) using R software was conducted. Single nucleotide polymorphisms (SNPs) related to the levels of various types of immune cells/cytokines and DCM were screened based on the genome-wide association studies (GWAS) obtained from open-source databases. The TSMR was conducted using inverse variance weighted (IVW), method, MR-Egger regression, weighted median method, and simple estimator based on mode to explore the causal association between the levels of each immune cell/cytokine and DCM. Sensitivity analysis was conducted using MR-Egger regression and a leave-one-out sensitivity test. A total of 1816 SNPs related to host immune status and DCM were identified. The IVW results showed a relationship between DCM and the circulating levels of basophils/eosinophils, total eosinophils-basophils, lymphocytes, and C-reactive protein (CRP). Increased lymphocytes levels (odds ratio (OR) = 0.91, 95% confidence interval (CI): 0.84-0.97, P = 0.005) were seen as protective against DCM, whereas increased basophil (OR = 1.18, 95% CI: 1.04-1.33, P = 0.022), eosinophil (OR = 1.1, 95% CI: 1.03-1.17, P = 0.007), eosinophil-basophil (OR = 1.09, 95% CI: 1.02-1.17, P = 0.014), and CRP (OR = 1.1, 95% CI: 1.03-1.18, P = 0.013) levels were associated with an increased risk of DCM. These analyses revealed that there may be a relationship between immune cells/select cytokine status and the onset of DCM. Future studies are required to further validate these outcomes in animal models and clinical trials.
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