Causal Relationship Between Immune Cells/Cytokines and Dilated Cardiomyopathy

Int Heart J. 2024;65(2):254-262. doi: 10.1536/ihj.23-215.

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.

Keywords: CRP; Eosinophil-basophil; Host immune status; Lymphocyte; Mendelian randomization analysis.

MeSH terms

  • Animals
  • C-Reactive Protein
  • Cardiomyopathy, Dilated* / genetics
  • Causality
  • Cytokines
  • Genome-Wide Association Study

Substances

  • C-Reactive Protein
  • Cytokines