Dataset Information

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

ABSTRACT:

Purpose of review

To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice.

Recent findings

Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at several institutions hold the promise of individualizing clopidogrel and warfarin based on genotype. Guidelines have been established to assist clinicians in prescribing clopidogrel or warfarin dose based on genotype. However, the clinical utility of clopidogrel and warfarin is still limited. Accordingly, large randomized clinical trials are underway to define the role of clopidogrel and warfarin pharmacogenetics in clinical practice.

Summary

Pharmacogenetics has offered compelling evidence toward the individualization of clopidogrel and warfarin therapies. The rapid advances in technology make the clinical implementation of clopidogrel and warfarin pharmacogenetics possible. The clinical genotyping programs and the ongoing clinical trials will help in overcoming some of the barriers facing the clinical implementation of clopidogrel and warfarin pharmacogenetics.

SUBMITTER: Shahin MH

PROVIDER: S-EPMC3731766 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Publications

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

Shahin Mohamed H A MH Johnson Julie A JA

Current opinion in cardiology 20130501 3

<h4>Purpose of review</h4>To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice.<h4>Recent findings</h4>Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at severa ...[more]

PMID: 23478884

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Project description:Warfarin is the most widely used oral anticoagulant in clinical practice. The cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) genotypes are associated with warfarin dose requirements in China. Accurate genotyping is vital for obtaining reliable genotype-guided warfarin dosing information. The current method for individualized dosing gene polymorphism detection for warfarin has the disadvantages of being easily contaminated, time-consuming, expensive, and unsuitable for clinical use. Herein, we present a novel application, a multiplex fluorescent melting curve assay of whole-blood direct amplification of nested polymerase chain reaction (PCR), to genotyping single-nucleotide polymorphism (SNPs) rapidly that affect warfarin efficacy. This method requires only 1 µL of whole blood, no DNA extraction, takes less than 2 h, costs less than $1, and is able to accurately distinguish between different SNP sites. Polymorphic loci were detected in whole blood specimens of 181 clinical warfarin-administered patients through nested blood direct PCR fluorescence melting curve analysis and gene sequencing. The results of the nested blood direct PCR multiplex fluorescence melting curve technology were 100% consistent with those of sequencing-characterized by high accuracy and high specificity. The allele frequencies were 94.5% for A and 5.5% for C at CYP2C9*3 (rs1057910), 7.5% for G and 92.5% for A at VKORC1 (rs9923231), and 77.1% for G and 22.9% for A at CYP4F2*3 (rs2108622). For CYP2C9*2 (rs1799853), only allele C was detected, with a frequency of 100%. Warfarin doses were lower in the CYP2C9*1*1 genotype population than in the CYP2C9*1*3 population, lower in the VKORC1 (AA) population than in the VKORC1 (GG) population, and higher in individuals with the CYP4F2*3 mutation (GA/AA) compared with those with wild-type (GG). In summary, the detection and genotyping of four polymorphic SNP sites using a multiplex fluorescent melting curve assay of whole blood direct amplification through nested PCR is highly importance for guiding personalized warfarin anticoagulant therapy.

Dataset Information

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

Purpose of review

Recent findings

Summary

Publications

Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

Similar Datasets

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