دورية أكاديمية
First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele
| العنوان: | First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele |
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| المؤلفون: | O'Brien, Travis J., Kidd, Robert S., Richard, Craig A.H., Ha, Ngoc Han, Witcher, Preston, Tran, Linda V., Barbour, April, Tuck, Matthew, McIntosh, Samantha D., Douglas, Jacqueline N., Harralson, Arthur F. |
| المصدر: | Medicine Faculty Publications |
| بيانات النشر: | Health Sciences Research Commons |
| سنة النشر: | 2013 |
| المجموعة: | George Washington University: Health Sciences Research Commons (HSRC) |
| مصطلحات موضوعية: | CYP2C9, Rs9332239, Warfarin |
| الوقت: | 12 |
| الوصف: | 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. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3962Test; https://doi.org/10.1016/j.cca.2013.05.008Test |
| DOI: | 10.1016/j.cca.2013.05.008 |
| الإتاحة: | https://doi.org/10.1016/j.cca.2013.05.008Test https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/3962Test |
| رقم الانضمام: | edsbas.2017305D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.cca.2013.05.008 |
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