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

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.