First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele
Clinica Chimica Acta
12; CYP2C9; Rs9332239; Warfarin
Background: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. Cases: Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4. ±. 7.94. mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2. ±. 12.65. mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. Conclusions: There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements. © 2013 Elsevier B.V.
O'Brien, T., Kidd, R., Richard, C., Ha, N., Witcher, P., Tran, L., Barbour, A., Tuck, M., McIntosh, S., Douglas, J., & Harralson, A. (2013). First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele. Clinica Chimica Acta, 424 (). http://dx.doi.org/10.1016/j.cca.2013.05.008