Genotyping ofCYP2C9andVKORC1in the Arabic Population of Al-Ahsa, Saudi Arabia

Abstract

Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies ofCYP2C9∗2 and∗3 andVKORC1–1639A alleles. However, the prevalence ofCYP2C9andVKORC1genetic variants is less characterized in Arab populations. A total of 131 healthy adult subjects from the Al-Ahsa region of Saudi Arabia were genotyped for theCYP2C9∗2 and∗3 andVKORC1–1639G>A polymorphisms by PCR-RFLP method. The frequencies of theCYP2C9∗2 and∗3 andVKORC1–1639A alleles were 13.3%, 2.3%, and 42.4%, respectively, with no subjects carrying 2 defective alleles. The frequencies of theCYP2C9∗3 andVKORC1–1639A alleles were significantly lower than those reported in different Arabian populations. None of the subjects with theVKORC1–1639AA genotype were carriers ofCYP2C9∗1/∗3 genotypes that lead to sensitivity to COAs therapy. The low frequency of theCYP2C9∗3 allele combined with the absence of subjects carrying 2 defectiveCYP2C9alleles suggests that, in this specific population, pharmacogenetic COAs dosing may mostly rely uponVKORC1genotyping.