ArticleActa pharmacologica Sinica2016
Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke.
Article in Acta pharmacologica Sinica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Pharmacodynamic assessment of prasugrel and clopidogrel in patients with non-cardioembolic stroke: a multicenter, randomized, active-control clinical trial.Journal of thrombosis and thrombolysis · 2020Trial
- Safety and Efficacy of Prasugrel in Elderly/Low Body Weight Japanese Patients with Ischemic Stroke: Randomized PRASTRO-II.Cerebrovascular diseases (Basel, Switzerland) · 2020Trial
- Recent Advances in Stroke Genetics-Unraveling the Complexity of Cerebral Infarction: A Brief Review.Genes · 2025Review
- Advances in the Clinical Use of Clopidogrel: A Review of Individualized Treatment Strategies and Monitoring Optimization Based on Genetic Polymorphisms.Pharmacogenomics and personalized medicine · 2025Review
- Influence of Genetic and Epigenetic Factors of P2YCardiovascular drugs and therapy · 2024Review
- Review
- Baseline P2Y12 reactivity, kidney function, and CYP2C19 genotype determine clopidogrel responsiveness in acute stroke.Scientific reports · 2023Article
- Association between P2Y1 and P2Y12 polymorphisms and acute myocardial infarction and ADP-induced platelet aggregation.BMC cardiovascular disorders · 2023Article
- Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer.Endocrinology and metabolism (Seoul, Korea) · 2022Review
- Cardiovascular Pharmacogenomics: An Update on Clinical Studies of Antithrombotic Drugs in Brazilian Patients.Molecular diagnosis & therapy · 2021Review
- Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.Clinical and translational science · 2021Observational
- Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial.Stroke and vascular neurology · 2021Article
- Multifactorial Background for a Low Biological Response to Antiplatelet Agents Used in Stroke Prevention.Medicina (Kaunas, Lithuania) · 2021Review
- Biomarkers for Antiplatelet Therapies in Acute Ischemic Stroke: A Clinical Review.Frontiers in neurology · 2021Review
- The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review.International journal of molecular sciences · 2020Review
- Clopidogrel Resistance in a Murine Model of Diet-Induced Obesity Is Mediated by the Interleukin-1 Receptor and Overcome With DT-678.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Impact of genetic variants of selected cytochrome P450 isoenzymes on pharmacokinetics and pharmacodynamics of clopidogrel in patients co-treated with atorvastatin or rosuvastatin.European journal of clinical pharmacology · 2020Article
- Clopidogrel responder status is uninfluenced by CYP2C19*2 in Danish patients with stroke.PloS one · 2020Observational
- Association between P2RY12 Gene Polymorphisms and IVIG Resistance in Kawasaki Patients.Cardiovascular therapeutics · 2020Article
- Influences of an NR1I2 polymorphism on heterogeneous antiplatelet reactivity responses to clopidogrel and clinical outcomes in acute ischemic stroke patients.Acta pharmacologica Sinica · 2019Observational
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThere is a high incidence of the antiplatelet drug clopidogrel resistance (CR) in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NR1I2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke.
methodsA total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NR1I2 (rs13059232), CYP3A4(*)1G (rs2242480), CYP2C19(*)2 (rs4244285) and P2RY12 (rs2046934) were genotyped.
resultsThe CR rate in this population was 36%. The CYP2C19(*)2 variant was a risk factor for CR ((*)2/(*)2+wt/(*)2 vs wt/wt, OR: 2.366, 95% CI: 1.180-4.741, P=0.014), whereas the CYP3A4(*)1G variant had a protective effect on CR ((*)1/(*)1 vs (*)1G/(*)1G+(*)1/(*)1G, OR: 2.360, 95% CI: 1.247-4.468, P=0.008). The NR1I2 (rs13059232) polymorphism was moderately associated with CR (CC vs TT+TC, OR: 0.533, 95% CI: 0.286-0.991, P=0.046). The C allele in P2RY12 (rs2046934) was predicted to be a protective factor for CR (CC+TC vs TT, OR: 0.407, 95% CI: 0.191-0.867, P=0.018). In addition, an association was found between hypertension and CR (P=0.022).
conclusionThe individuals with both the CYP2C19(*)2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4(*)1G allele, P2RY12 (rs2046934) C allele and NR1I2 (rs13059232) CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.
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