p450 - publications

Predict more p450 - ligand interactions now!


1. Int J Lab Hematol. 2012 Apr 26. doi: 10.1111/j.1751-553X.2012.01426.x. [Epub
ahead of print]

Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and
their influence on warfarin maintenance dose: proposal for a new dosing regimen.

El Din MS, Amin DG, Ragab SB, Ashour EE, Mohamed MH, Mohamed AM.

Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo,
Egypt Clinical and Chemical Pathology, Faculty of Medicine, Fayoum University,
Fayoum, Egypt Consultant of Cardiology, National Heart Institute, Cairo, Egypt.

Introduction:  Warfarin is one of the most widely used anticoagulants, yet
interindividual differences in drug response, a narrow therapeutic range and a
high risk of bleeding or stroke complicate its use. We aimed to determine the
allele and genotype frequency of VKORC1 1173 C>T, CYP2C9*2 and CYP2C9*3 variant
polymorphisms in the Egyptian population and to evaluate their influence on the
interindividual differences in warfarin dosage. Methods:  A total of 154
unrelated healthy adult patients and 46 warfarin-treated patients were included.
SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for
studying VKORC1 (C1173T) and CYP2C9*3 polymorphisms. Mutagenically separated PCR
assay was used to detect the CYP2C9*2 allele. Results:  VKORC1 genotype
frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence
of CYP2C9 haplotypes was 81% (*1\*1), 3.3% (*1\*2), 9.7% (*1\*3), 4.5% (*2\*2)
and 0.65% (2\*3 and *3\*3). VKORC1 TT and CYP2C9*2\*2 were associated with a
significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and
15.6% of warfarin dose variability, respectively, and together with clinical
factors explained 61.3% of total variability. Conclusion:  VKORC1-TT and CYP2C9
*1/*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT
genotype required a lower warfarin dose.

© 2012 Blackwell Publishing Ltd.

PMID: 22533669 [PubMed - as supplied by publisher]