SynthesisJournal of thrombosis and thrombolysis2016
PON1 Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics, pharmacodynamics, and a meta-analysis of clinical outcomes.
Synthesis in Journal of thrombosis and thrombolysis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- Trial
- A narrative review of research advancements in pharmacogenetics of cardiovascular disease and impact on clinical implications.NPJ genomic medicine · 2025Review
- Review
- Pharmacogenomics of Cardiovascular Drugs for Atherothrombotic, Thromboembolic and Atherosclerotic Risk.Genes · 2023Review
- Pharmacogenetics of Antiplatelet Therapy.Annual review of pharmacology and toxicology · 2023Review
- Pharmacogenetics to guide cardiovascular drug therapy.Nature reviews. Cardiology · 2021Review
- Impact of selected genetic factors on clopidogrel inactive metabolite level and antiplatelet response in patients after percutaneous coronary intervention.Pharmacological reports : PR · 2021Article
- Article
- Association of PON1 gene promoter DNA methylation with the risk of Clopidogrel resistance in patients with coronary artery disease.Journal of clinical laboratory analysis · 2019Article
- Effects of PON1 Gene Promoter DNA Methylation and Genetic Variations on the Clinical Outcomes of Dual Antiplatelet Therapy for Patients Undergoing Percutaneous Coronary Intervention.Clinical pharmacokinetics · 2018Article
- Pharmacogenetic association study on clopidogrel response in Puerto Rican Hispanics with cardiovascular disease: a novel characterization of a Caribbean population.Pharmacogenomics and personalized medicine · 2018Article
- Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance.Vascular health and risk management · 2018Review
- Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives.International journal of environmental research and public health · 2017Review
- Tailoring of medical treatment: hemostasis and thrombosis towards precision medicine.Haematologica · 2017Article
- Minorities Are Underrepresented in Clinical Trials of Pharmaceutical Agents for Cystic Fibrosis.Annals of the American Thoracic Society · 2016Article
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Authors and funding
18 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clopidogrel and prasugrel are antiplatelet therapies commonly used to treat patients with cardiovascular disease. They are both pro-drugs requiring biotransformation into active metabolites. It has been proposed that a genetic variant Q192R (rs662 A>G) in PON1 significantly alters the biotransformation of clopidogrel and affects clinical outcomes; however, this assertion has limited support. The relationship between this variant and clinical outcomes with prasugrel has not been studied. We genotyped PON1 Q192R in 275 healthy subjects treated with clopidogrel or prasugrel and 2922 patients with an ACS undergoing PCI randomized to treatment with clopidogrel or prasugrel in the TRITON-TIMI 38 trial. A meta-analysis was performed including 13 studies and 16,760 clopidogrel-treated patients. Among clopidogrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.62) or change in platelet aggregation (P = 0.51). Consistent with these results, in clopidogrel-treated patients in TRITON-TIMI 38, there was no association between Q192R and the rates of CV death, myocardial infarction, or stroke (RR 11.2 %, QR 8.6 %, and QQ 9.3 %; P = 0.66) or stent thrombosis (RR 2.4 %, QR 0.7 %, and QQ 1.6 %, P = 0.30), with patients with the putative at-risk Q variant having numerically lower event rates. Likewise, among prasugrel-treated subjects, there were no associations between Q192R and active drug metabolite levels (P = 0.88), change in platelet aggregation (P = 0.97), or clinical outcomes (P = 0.72). In a meta-analysis, the Q variant was not significantly associated with MACE (QQ vs. RR 1.22, 95 % CI 0.84-1.76) or stent thrombosis (QQ vs. RR OR 1.36, 95 % CI 0.77-2.38). Furthermore, when restricted to the validation studies, the OR (95 % CI) for MACE and stent thrombosis were 0.99 (0.77-1.27) and 1.23 (0.74-2.03), respectively. In the present study, the Q192R genetic variant in PON1 was not associated with the pharmacologic or clinical response to clopidogrel, nor was it associated with the response to prasugrel. The meta-analysis reinforced a lack of a significant association between Q192R and cardiovascular outcomes in clopidogrel-treated patients.
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