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Analysis of spermidine's effect on coronary heart disease risk using bidirectional Mendelian randomization and
Tianyi Wang1, Li Lin1, Yaodong Ding1
1Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, 100011, China.
Background:
This study examines the causal relationship between spermidine levels and coronary artery disease (CHD) risk using a bidirectional Mendelian Randomization (MR) approach.
Methods:
We employed genetic variants as instrumental variables to assess the influence of genetically predicted spermidine levels on CHD risk and vice versa. Data for the MR analysis were sourced from the UK Biobank and genome-wide association study datasets, focusing on single nucleotide polymorphisms (SNPs) associated with spermidine levels and CHD. The study also utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) for accurate quantification of spermidine in plasma samples.
Results:
Our analysis identified a significant association between lower genetically predicted spermidine levels and increased CHD risk. The LC-MS/MS results supported the accurate measurement of spermidine, highlighting its feasibility as a clinical biomarker.
Conclusions:
The findings suggest that reduced spermidine levels may be a significant risk factor for CHD. This study supports the potential of spermidine as a biomarker for CHD risk assessment and its development as a therapeutic target. The integration of genetic and biochemical methodologies enhances our understanding of the role of spermidine in cardiovascular health and its utility in managing CHD risk.

