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Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose.
- Source :
-
American journal of clinical pathology [Am J Clin Pathol] 2008 Jun; Vol. 129 (6), pp. 876-83. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Anticoagulants pharmacokinetics
Cytochrome P-450 CYP2C9
DNA Mutational Analysis
Dose-Response Relationship, Drug
Genotype
Humans
Reproducibility of Results
Sequence Analysis, DNA
Vitamin K Epoxide Reductases
Warfarin pharmacokinetics
Anticoagulants therapeutic use
Aryl Hydrocarbon Hydroxylases genetics
Mixed Function Oxygenases genetics
Pharmacogenetics methods
Polymorphism, Single Nucleotide
Warfarin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9173
- Volume :
- 129
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of clinical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 18480003
- Full Text :
- https://doi.org/10.1309/1E34UAPR06PJ6HML