title: An instructive case suggesting warfarin resistance which is independent on the regulation of the CYP2C9 and VKORC1 genotype.
abstract: To improve the safety and effectiveness of warfarin (WF) therapy, the initial dose trends to be practically decided based on single nucleotide polymorphism (SNP) genotyping of two genes, cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex1 (VKORC1). We encountered a 43-year-old female who was hospitalized for investigation and treatment because of intermittent convulsive seizures. Right brain cortical vein thrombi were confirmed by magnetic resonance imaging (MRI) scan; therefore, a 3 mg dose of WF was empirically initiated. The prothrombin time (PT), expressed as the international normalized ratio (INR), did not change at all, even when WF was increased to a dose of 11 mg/day. Direct sequence analysis revealed *3 in CYP2C9 and 3673 GA, 6484 CT, 6853 GC and 9041 GA in VKORC1, indicating that the genotypic pattern of the two genes is the responsible SNP for the moderate phenotype on WF sensitivity. Conclusively, our case may present an unknown mechanism other than the concern mentioned above.
authors.affiliation: Department of Clinical Laboratory, Nagasaki University Hospital, Nagasaki 850-8501, Japan. fumitaka@nagasaki-u.ac.jp
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Nishimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tokuda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sasaki
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mori
authors.forename: Kazuto
authors.initials: K
authors.lastname: Tsuruda
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002550:Cerebral Veins; D065729:Cytochrome P-450 CYP2C9; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D020767:Intracranial Thrombosis / Q000175:diagnosis / Q000188:drug therapy; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012640:Seizures / Q000209:etiology; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: 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