Role of immune cells in mediating the effect of triacylglycerol (50:2) on hypotension

Abstract

Objective To explore the causal relationship between genetically predicted triglyceride (TG) levels and the risk of hypotension under the mediation of immune cells using a two-step Mendelian randomization (MR) approach. Methods We utilized summary data from genome-wide association studies (GWAS) and information from the FinnGen database to select single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). A two-step MR analysis was conducted on genetically predicted hypotension (including 4924 cases and 406223 controls), employing methods such as inverse variance weighting (IVW), MR-Egger regression, and sensitivity analysis to ensure the accuracy and robustness of the results. Results Genetically predicted TG was found to be positively associated with the risk of hypotension (for each 1 SD increase, the risk of hypotension increased by 21.1%, OR = 1.211; 95% CI = 1.085–1.352, P < 0.001, IVW method), with immune cells CD25 + + CD8br AC (mediation effect ratio = 7.223%) and IgD + CD38dim %B cell (mediation effect ratio = 5.730%) acting as mediators. The above MR analyses did not exhibit heterogeneity and pleiotropy. Conclusion Our study provides a new perspective for a deeper understanding of the causal relationship between lipid metabolism pathways and the risk of hypotension. This includes optimizing dietary structure and improving the health of the immune system to prevent the occurrence of hypotension, or using CD25 + + CD8br AC and IgD + CD38dim %B cell as biomarkers for hypotension to identify individuals at potential risk early on, providing new possibilities for targeted treatment. This can contribute to providing more precise and personalized strategies for the diagnosis, treatment, and management of patients with hypotension. Additionally, further research is needed to validate our findings.