title: Warfarin pharmacogenomics: recommendations with available patented clinical technologies.
abstract: Warfarin pharmacogenomic testing has become a prime example of the utility of personalized molecular testing in the modern clinical laboratory. Warfarin is a commonly used drug for the prevention and treatment of thromboembolic complications in a variety of clinical situations. However, a number of factors lead to a high interindividual variability in dose requirements. Among the primary factors in this variability are genetic polymorphisms in general patient populations, which can account for 35-50% of varying dose requirements among patients. In this review, we discuss the implications of polymorphisms in the cytochrome P-450 enzyme 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Enzyme Complex subunit 1 (VKORC1) as they relate to therapeutic warfarin dosing. We discuss the clinical utility of pharmacogenomics testing as related to warfarin dosing, and propose a clinical model for the implementation of the pharmacogenomic test results. Finally, we provide a brief overview of the currently available commercial testing platforms with discussion of the complexities of utilizing patented methodologies in bringing genetic testing such as this to the clinical laboratory.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Borkowski
authors.forename: Avni
authors.initials: A
authors.lastname: Kardani
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Mastorides
authors.affiliation: P&LMS (113), 13000 Bruce B. Downs Blvd, Tampa, FL 33612, USA. Andrew.borkowski@va.gov.
authors.forename: L Brannon
authors.initials: LB
authors.lastname: Thomas
mesh_terms: D000925:Anticoagulants / Q000378:metabolism / Q000627:therapeutic use*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics / Q000378:metabolism; D060005:Genotyping Techniques; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D010330:Patents as Topic; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D013923:Thromboembolism / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D064417:Vitamin K Epoxide Reductases / Q000235:genetics / Q000378:metabolism; D014859:Warfarin / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases