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Serum metabolites and hypercholesterolemia: insights from a two-sample Mendelian randomization study
Weitao Wang1, Jingwen Qiao2, Zhaoyin Su1
1The First Clinical College of Medicine, Lanzhou University, Lanzhou, China.
Frontiers in Cardiovascular Medicine
|August 22, 2024
Summary
This study identifies key serum metabolites linked to hypercholesterolemia risk and protection. Findings reveal potential causal relationships and metabolic pathways, offering new therapeutic targets for cardiovascular disease prevention.
Area of Science:
- Metabolomics
- Genetics
- Cardiovascular Disease Research
Background:
- Hypercholesterolemia is a major risk factor for cardiovascular disease.
- The precise relationship between serum metabolites and hypercholesterolemia pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the association between serum metabolites and hypercholesterolemia using genetic data.
- To identify specific metabolites and metabolic pathways involved in hypercholesterolemia.
Main Methods:
- Utilized Genome-Wide Association Studies (GWAS) data from a European population.
- Applied Mendelian Randomization (MR) and KEGG pathway enrichment analysis.
- Analyzed 486 serum metabolites in individuals with hypercholesterolemia.
Main Results:
- Ten metabolites showed significant associations with hypercholesterolemia.
- 2-methoxyacetaminophen sulfate and 1-oleoylglycerol were risk-enhancing.
- 3-(cystein-S-yl)acetaminophen, hydroquinone sulfate, and 2-hydroxyacetaminophen sulfate showed protective effects.
- Identified eight critical metabolic pathways, including amino acid and pyruvate metabolism.
Conclusions:
- Established potential causal links between specific serum metabolites and hypercholesterolemia.
- Highlighted the role of identified metabolic pathways in disease development.
- Suggests these metabolites and pathways as potential targets for novel therapeutic interventions.
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