Characterization of Three CYP2C19 Gene Variants by MassARRAY and Point of Care Techniques: Experience from a Czech Centre

Petřek, Martin; Kocourková, Lenka; Žižková, Veronika; Nosek, Zdenek; Táborský, Miloš; Petrkova, Jana

doi:10.1007/s00005-016-0440-8

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…Genomic DNA was extracted from 0.5 mL of peripheral blood drawn into EDTA‐coated tubes using QIAamp DNA Blood Mini Kit (Qiagen, Germany). Three single nucleotide polymorphisms (SNPs)—CYP2C19*2 (rs4244285), *3 (rs4986893) and *17 (rs12248560)—were genotyped using Sequenom MassARRAY platform integrating iPLEX (Sequenom Inc, San Diego, CA, USA) based on a previously described method 29 . The assay consists of an initial locus‐specific polymerase chain reaction amplification followed by single base extension reaction using mass‐modified dideoxynucleotide terminators of an oligonucleotide primer that anneals immediately upstream of the target polymorphic site.…”

Section: Methodsmentioning

confidence: 99%

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y₁₂ inhibitor

Zhang

Zhu

Zhan

et al. 2020

Brit J Clinical Pharma

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Aims We investigated the impacts of CYP2C19 polymorphisms on pharmacokinetics and pharmacodynamics of vicagrel in healthy Chinese subjects. Methods CYP2C19 extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs; 16 subjects/group) participated in a randomized, open‐label, 2‐period cross‐over study. Each study period lasted 7 days, with a loading dose of 24 mg of vicagrel or 300 mg of clopidogrel on day 1, and maintenance doses of 6 mg of vicagrel or 75 mg of clopidogrel daily from day 2 to day 7. The pharmacokinetics and pharmacodynamics were assessed on day 1 and day 7. Results After a loading dose, the AUC0‐t of the active metabolite H4 by vicagrel was slightly lower in IMs and PMs (decreased by 21 and 27%, respectively) compared to EMs. Similar results were found after maintenance doses. In EMs, the AUC0‐t of H4 by vicagrel was somewhat higher than clopidogrel after the loading dose, and comparable with clopidogrel (90% confidence interval 0.94, 1.21) after the maintenance doses. However, it was much higher than clopidogrel in PMs, with a 1.28‐fold (loading dose) and a 73% (maintenance doses) increases compared to clopidogrel (P < 0.001). Consequently, the inhibition of platelet aggregation by vicagrel was greater than clopidogrel after both loading dose (28.2 vs 12.4% at 4 hours, P < 0.01) and maintenance doses (42.8 vs 24.6% at 4 hours, P < 0.001) in PMs. Conclusions CYP2C19 polymorphisms have less impact on vicagrel as compared to clopidogrel. Drug exposure and response to vicagrel in PMs were even higher than to clopidogrel in IMs.

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Section: Methodsmentioning

confidence: 99%

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y₁₂ inhibitor

Zhang

Zhu

Zhan

et al. 2020

Brit J Clinical Pharma

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“…In some acute care settings, it may be important for a quick turnaround time to physically perform the test using an instrument that is in a clinic or inpatient unit. There are a few examples, such as anticipating the need for clopidogrel antiplatelet therapy after percutaneous coronary intervention, when the availability of quick turnaround times in or near the coronary procedure room could facilitate prescribing decisions needed the same day as the procedure (31,102,105,114). Point-of-care testing has also been employed for warfarin (analyzing variants in CYP2C9 and VKORC1), another example when decisions about prescribing and dosing the medication are somewhat urgent (46).…”

Section: Reactive Testingmentioning

confidence: 99%

Advancing Pharmacogenomics from Single-Gene to Preemptive Testing

Haidar

Crews

Hoffman

et al. 2022

Annu. Rev. Genom. Hum. Genet.

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Pharmacogenomic testing can be an effective tool to enhance medication safety and efficacy. Pharmacogenomically actionable medications are widely used, and approximately 90–95% of individuals have an actionable genotype for at least one pharmacogene. For pharmacogenomic testing to have the greatest impact on medication safety and clinical care, genetic information should be made available at the time of prescribing (preemptive testing). However, the use of preemptive pharmacogenomic testing is associated with some logistical concerns, such as consistent reimbursement, processes for reporting preemptive results over an individual's lifetime, and result portability. Lessons can be learned from institutions that have implemented preemptive pharmacogenomic testing. In this review, we discuss the rationale and best practices for implementing pharmacogenomics preemptively. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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“…Regarding cardiovascular setting, CYP gene variation plays role in warfarin and clopidogrel metabolism with clear clinical relevance (e.g. [30]). In context of statin adverse drug reaction, Mulder et al [22] reported higher incidence of statin intolerance in the group of patients who carried two of the less effective CYP2D6 *3,*4,*5 alleles.…”

Section: Family Of Cytochrome P450 Genesmentioning

confidence: 99%

Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance

Petrkova¹,

Táborský²,

Petřek³

2018

Genetic Diversity and Disease Susceptibility

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Statins are very effective for lowering low-density lipoprotein cholesterol for primary and secondary cardiovascular disease prevention. While statins are usually well tolerated, individual response to statin therapy varies and intolerance, predominantly muscle symptoms, may appear in a significant proportion of patients. Besides clinical factors, variation in genes coding for proteins with drug transporting, immune or enzymatic function have been implicated in the pathogenesis of statin intolerance. In this review, we will characterise the candidate gene variants for development of statin intolerance, describe their population distribution and summarise current knowledge on their biological plausibility. Clinical relevance and current guidelines/recommendations will be also discussed.By analogy to individual nature of patients´ response to treatment [8][9][10] there are also interindividual differences in occurrence and extent of statin intolerance and its symptoms. The knowledge of the risk factors predisposing for intolerance development including characteristic genetic background is crucial for its understanding and prevention. In this chapter we will review the polymorphic gene variants implicated in development of statin intolerance, briefly describe their biological plausibility and characterise clinical relevance. Statin intoleranceStatin intolerance is the inability to tolerate sufficient dose of statin needed to reduce cardiovascular risk due to side effects or intolerance to treatment [11]. The most frequent are muscle symptoms characterised bellow. Statin-associated muscle symptomsStatin-induced muscle symptoms range from myalgia to mild or severe myopathy and even to rare rhabdomyolysis [12]. The symptoms appear in about 75% in the first 10-12 weeks and in 90% of cases in the first 6 months after treatment initiation or dose up titration [13]. The true frequency muscle related side effects has been widely debated: while an observational study reported as much as about 20% of patients on statins [14], clinical trial data suggests frequencies to be equal or lower than 5% [15], however there was a study reporting that clinical trials did not use a standard definition for statin myalgia [16], which may result in underestimated occurrence of statin-induced muscle symptoms. In any case, given very high usage of statins (the third most frequently prescribed drug), even lower relative frequency numbers would mean substantial absolute number of symptomatic patients. Clinical-related risk factorsThe available data shows that the side effects of statin therapy are group-dependent, timedependent and dose-dependent; their frequency is greater at a higher statin dose [17].Endogenous factors known to increase occurrence of side effects are as follows: another lipid-lowering therapy, alcohol abuse, surgery, heavy exercise. Importantly, interactions with medication may be serious [18]; particularly drug interactions likely contribute the susceptibility to statin related muscle symptoms [19].Further factors predisposi...

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Characterization of Three CYP2C19 Gene Variants by MassARRAY and Point of Care Techniques: Experience from a Czech Centre

Cited by 8 publications

References 24 publications

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y₁₂ inhibitor

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y₁₂ inhibitor

Advancing Pharmacogenomics from Single-Gene to Preemptive Testing

Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance

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Characterization of Three CYP2C19 Gene Variants by MassARRAY and Point of Care Techniques: Experience from a Czech Centre

Cited by 8 publications

References 24 publications

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12 inhibitor

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y12 inhibitor

Advancing Pharmacogenomics from Single-Gene to Preemptive Testing

Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance

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Product

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Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y₁₂ inhibitor

Impacts of CYP2C19 genetic polymorphisms on bioavailability and effect on platelet adhesion of vicagrel, a novel thienopyridine P2Y₁₂ inhibitor