p450 - publications

Predict more p450 - ligand interactions now!

1. Rinsho Byori. 2011 Dec;59(12):1087-90.

An instructive case suggesting warfarin resistance which is independent on the
regulation of the CYP2C9 and VKORC1 genotype.

Nishimura F, Tokuda M, Sasaki D, Mori S, Tsuruda K, Hasegawa H, Yanagihara K,
Kamihira S.

Department of Clinical Laboratory, Nagasaki University Hospital, Nagasaki
850-8501, Japan. fumitaka@nagasaki-u.ac.jp

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.

PMID: 22338910 [PubMed - in process]