ArticleCardiovascular drugs and therapy2021
Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics.
Article in Cardiovascular drugs and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Synergistic Interaction Between PEAR1-FGB and the Dominant Role of ABCB1 in Thrombosis Risk: A SHAP and MDR-Based Study in Vietnamese Pedigrees.Journal of blood medicine · 2026Article
- Analysis of the effect of CYP2C19 gene properties on the anti-platelet aggregation of clopidogrel after carotid artery stenting under network pharmacology.BMC pharmacology & toxicology · 2024Article
- Pharmacogenetics of Antiplatelet Therapy.Annual review of pharmacology and toxicology · 2023Review
- Targeted haplotyping in pharmacogenomics using Oxford Nanopore Technologies' adaptive sampling.Frontiers in pharmacology · 2023Article
- Race and Drug Toxicity: A Study of Three Cardiovascular Drugs with Strong Pharmacogenetic Recommendations.Journal of personalized medicine · 2021Article
- Pharmacogenomics education, research and clinical implementation in the state of Minnesota.Pharmacogenomics · 2021Review
- A Pharmacogenetic Study ofJournal of personalized medicine · 2021Article
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
Abstract
purposeDescribe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.
methodsSeventy ST cases on clopidogrel identified from the PLATO trial (n = 58) and Mayo Clinic biorepository (n = 12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.
resultsPoor metabolizers (n = 4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n = 29) than controls (n = 18). Functional studies of CYP2C19 exonic variants (n = 11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n = 169) compared with controls (n = 84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases.
conclusionNGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.
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