Key result
Genetic variants in DNAH17, PGS1, and ABCA1 were associated with the antiplatelet effect of ticagrelor, while age, sex, and platelet count were potential factors for bleeding events.
Why the study?
Predictive biomarkers for ticagrelor are lacking, especially in Chinese patients, making it important to study individual differences in antiplatelet efficacy and safety through pharmacogenomics.
Observational (n=100)
Genetic variants in DNAH17, PGS1, and ABCA1, along with clinical factors like age and sex, may influence ticagrelor efficacy and bleeding risk in Chinese patients post-PCI.
Answers are grounded in this paper and cite their sources.
Supports further pharmacogenomic investigation of ticagrelor in Chinese patients; leaves open clinical translation pending validation.
BACKGROUND: Generally, many individual factors can affect the clinical application of drugs, of which genetic factors contribute more than 20%. Ticagrelor is a new class of receptor inhibitors receptor antagonist of P2Y12 and is used as an antiplatelet agents. But it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through pharmacogenomics research. METHODS: Whole-exome sequencing (WES) was performed in 100 patients after PCI with ticagrelor treatment. Clinical characteristics and WES of patients were used to performed genome-wide association analysis (GWAS), region-based tests of rare DNA variant to find the influencing factors of antiplatelet effect to ticagrelor and bleeding events. Co-expression, protein-protein interaction (PPI) network and pathway enrichment analysis were then used to find possible genetic mechanisms. Atlas of GWAS (https://atlas.ctglab.nl/) were used for external data validation. RESULTS: DNAH17, PGS1 and ABCA1 as the potential variant genes are associated with the expected antiplatelet effect to ticagrelor. The affected pathways may include the synthesis and metabolism of lipoprotein cholesterol and the catabolic process of pyrimidine-containing compound (GO:0072529). Age, sex and PLT were found may be potential factors for ticagrelor bleeding events. CONCLUSION: We systematically identified new genetic variants and some risk factors for reduced efficacy of ticagrelor and highlighted related genes that may be involved in antiplatelet effects and bleeding event of ticagrelor. Our results enhance the understanding of the absorption and metabolic mechanisms that influence antiplatelet response to ticagrelor treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161002. First Posted: May 19, 2017. https://clinicaltrials.gov/ct2/show/study/NCT03161002.
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A 2022 study conducted an observational in Post-percutaneous coronary intervention (PCI) (n=100). Genetic variants (DNAH17, PGS1, ABCA1) was evaluated on Antiplatelet effect to ticagrelor and bleeding events. Genetic variants in DNAH17, PGS1, and ABCA1 were associated with the antiplatelet effect of ticagrelor, while age, sex, and platelet count were potential factors for bleeding events.
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