Genetic polymorphism of CYP2C9 and VKORC1 in the Nigerian population: significance for warfarin therapy in the population

Abstract

I n t r o d u c t i o n : CYP2C9 and VKORC1 are important pharmacogenes for warfarin dosing. Variability in response to warfarin therapy, which may carry fatal consequences, have been explained by the presence of functionally relevant variants of these genes.A i m : This study investigated the prevalence and highlights the clinical implications of some relevant variants of CYP2C9 and VKORC1 in the Nigerian population as they affect the safe administration of warfarin. M a t e r i a l a n d m e t h o d s : Genotype analysis via a Sequenom iPLEX platform and direct Sanger sequencing was carried out in 158 healthy, unrelated subjects, drawn from the main Nigerian ethnicities. The alleles screened for comprised CYP2C9*2 (rs1799853), *3 (rs1057910) and *8 (rs7900194). Subjects were also genotyped for VKORC1*3 (rs7294) allele. R e s u l t s a n d d i s c u s s i o n : All the studied alleles were in Hardy-Weinberg equilibrium, and CYP2C9*8 was the most prevalent CYP2C9 allele with a frequency of 0.073 in the population. The other CYP2C9 alleles, CYP2C9*2 and *3, occurred at frequencies of 0.006 and 0.003, respectively. VKORC1*3, however, was observed at a frequency of 0.437. C o n c l u s i o n s : Although all alleles detected in the population are significantly related to warfarin dosing, VKORC1*3 might be the most critical owing to its high prevalence (108 out of 158) across individuals from different Nigerian ethnicities. Plasma warfarin-level monitoring may also be desirable in instances where individuals carry both the CYP2C9*8 and VKORC1*3 alleles, an occurrence observed in 9% of the studied individuals.