title: Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose.
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.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Cristi R
authors.initials: CR
authors.lastname: King
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Porche-Sorbet
authors.forename: Brian F
authors.initials: BF
authors.lastname: Gage
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Yannick
authors.initials: Y
authors.lastname: Renaud
authors.forename: Michael S
authors.initials: MS
authors.lastname: Phillips
authors.forename: Charles
authors.initials: C
authors.lastname: Eby
mesh_terms: D000925:Anticoagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases