Abstract

Pathare AV, Alzadjali S, Misquith R, Alkindi S, Sahaya P, Paldi A and Krishnamoorthy R

There are significant differences in the performances of dosing algorithms between Caucasians, African Americans and Oriental populations owing to differences in the prevalence of genetic polymorphisms in enzymes involved in the pharmacokinetic and pharmacodynamic pathway, although other non-genetic factors do also contribute. The purpose of this work was to assess the vitamin K-epoxide reductase complex unit 1 (VKORC1) haplotypes in the Omani population for predicting specificity of warfarin dose response. We studied the pattern of five single nucleotide polymorphisms (SNPs) (rs 9923231; rs 9934438; rs 2884737; rs 17708472 and rs 7294) that define the VKORC1 haplotypes in healthy adult Omani subjects using a PCR-based targeted genomic DNA sequencing. The observed frequencies for VKORC1*1, *2,*3,*4 haplotypes were 0.08, 0.28, 0.29, 0.14 respectively. Four different novel haplotypes were found, two of which were present at a frequency above 3% in the Omani subjects. This is the first study to establish the VKORC1 haplotypes in Omanis. The predicted prevalence of warfarin sensitive VKORC1*2 haplotype was 27.8%, whereas it was 29.4 and 14.4% respectively for the haplotypes *3 and *4. The significant presence of VKORC1*1 haplotype (8%) in Omanis, (otherwise quite rare in Caucasians and Asians) can be traced back to their ancestral African admixture.