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Association Between Ticagrelor and Glucose Homeostasis Regulation: Insights from Genetic and Transcriptomic Analyses
Zhipeng Xie1, Heshuo Ma2, Yingjian Liu3
1Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. xiezp1115@163.com.
Biochemical Genetics
|May 20, 2026
Summary
Ticagrelor offers therapeutic benefits for diabetes patients with acute coronary syndrome. This study reveals ticagrelor
Area of Science:
- Pharmacology
- Genetics
- Metabolomics
Background:
- Ticagrelor is beneficial for acute coronary syndrome (ACS) patients with diabetes.
- The mechanisms behind ticagrelor's benefits in diabetic ACS patients are not fully understood.
Purpose of the Study:
- To investigate the underlying mechanisms of ticagrelor's therapeutic benefits in diabetic ACS patients.
- To identify potential causal mediator proteins and molecular pathways involved in glucose metabolism.
Main Methods:
- Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data.
- Plasma proteomics and type 2 diabetes data.
- RNA sequencing (RNA-seq) of ticagrelor-treated HepG2 cells.
Main Results:
- Genetically proxied ticagrelor significantly reduced diabetes risk (OR=0.859).
- Upregulation of BDH2 protein mediated 24.41% of this effect.
- Ticagrelor enhanced glucose consumption in vitro, involving mitochondrial respiration and ATP biosynthesis.
Conclusions:
- Ticagrelor exhibits non-platelet functions that contribute to maintaining glucose homeostasis.
- Findings suggest potential for ticagrelor repurposing for managing glucose metabolism.
- BDH2 protein and mitochondrial pathways are key mediators of ticagrelor's glucose-lowering effects.
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