Performance of Commercial Platforms for Rapid Genotyping of Polymorphisms Affecting Warfarin Dose
| Autor: | Cristi R. King, Rhonda Porche-Sorbet, Paul M. Ridker, Brian F. Gage, Yannick Renaud, Michael S. Phillips, Charles S. Eby |
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| Rok vydání: | 2008 |
| Předmět: |
Oncology
medicine.medical_specialty Genotype DNA Mutational Analysis Biology Pharmacology Polymorphism Single Nucleotide Mixed Function Oxygenases Vitamin K Epoxide Reductases Internal medicine medicine Humans Genotyping CYP2C9 Cytochrome P-450 CYP2C9 Dose-Response Relationship Drug Warfarin Anticoagulants Reproducibility of Results Sequence Analysis DNA General Medicine Molecular diagnostics Vitamin-K-epoxide reductase (warfarin-sensitive) Pharmacogenetics Pyrosequencing Vitamin K epoxide reductase Aryl Hydrocarbon Hydroxylases VKORC1 medicine.drug |
| Zdroj: | American Journal of Clinical Pathology. 129:876-883 |
| ISSN: | 1943-7722 0002-9173 |
| DOI: | 10.1309/1e34uapr06pj6hml |
| Popis: | Initiation of warfarin therapy is associated with bleeding owing to its narrow therapeutic window and unpredictable therapeutic dose. Pharmacogenetic-based dosing algorithms can improve accuracy of initial warfarin dosing but require rapid genotyping for cytochrome P-450 2C9 (CYP2C9) *2 and *3 single nucleotide polymorphisms (SNPs) and a vitamin K epoxide reductase (VKORC1) SNP. We evaluated 4 commercial systems: INFINITI analyzer (AutoGenomics, Carlsbad, CA), Invader assay (Third Wave Technologies, Madison, WI), Tag-It Mutation Detection assay (Luminex Molecular Diagnostics, formerly Tm Bioscience, Toronto, Canada), and Pyrosequencing (Biotage, Uppsala, Sweden). We genotyped 112 DNA samples and resolved any discrepancies with bidirectional sequencing. The INFINITI analyzer was 100% accurate for all SNPs and required 8 hours. Invader and Tag-It were 100% accurate for CYP2C9 SNPs, 99% accurate for VKORC1 -1639/3673 SNP, and required 3 hours and 8 hours, respectively. Pyrosequencing was 99% accurate for CYP2C9 *2, 100% accurate for CYP2C9 *3, and 100% accurate for VKORC1 and required 4 hours. Current commercial platforms provide accurate and rapid genotypes for pharmacogenetic dosing during initiation of warfarin therapy. |
| Databáze: | OpenAIRE |
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