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Allele and genotype frequencies of the two single nucleotide polymorphisms in the VKORC1 gene that are most important for warfarin treatment among Emiratis
Warfarin is the most widely prescribed anticoagulant worldwide. However, warfarin doses vary up to 20-fold and side-effects (at high doses) or therapy failure (at lower doses) are major risks of treatment. The target enzyme of warfarin, vitamin K epoxide reductase complex 1 (VKORC1), is encoded by the highly polymorphic VKORC1 gene and gene polymorphisms contributes to approximately 30% of the variability in dose. In this study, we used polymerase chain reaction (PCR) and direct DNA sequencing to genotype the two most clinically important variants (rs9923231 and rs7294) of the VKORC1 gene among Emiratis. We genotyped 117 healthy Emirati nationals and found that the frequencies of the rs9923231 genotypes GG, GA and AA are 0.256, 0.496 and 0.248, respectively. The frequency of the G allele for this single nucleotide polymorphism (SNP) is 0.504 while the frequency of the A allele is 0.496. However, the frequencies of the rs7294 GG, GA and AA genotypes are 0.462, 0.393 and 0.145, respectively. The alleles frequencies for this SNP were 0.660 for the G allele and 0.340 for the A allele. Genotypes and allele frequencies of the two studied SNPs were found to be different between the Emirati population studied and Indian and Chinese populations; however, they were similar to the frequencies found in Caucasians and other regional populations, such as the Saudis, Turkish and Iranians. These findings are potentially important for determining the starting warfarin dose for Emirati patients requiring anticoagulant treatment.