title: Genotyping of CYP2C9 and VKORC1 in 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 of CYP2C9*2 and *3 and VKORC1 -1639A alleles. However, the prevalence of CYP2C9 and VKORC1 genetic 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 the CYP2C9 *2 and *3 and VKORC1 -1639G>A polymorphisms by PCR-RFLP method. The frequencies of the CYP2C9 *2 and *3 and VKORC1 -1639A alleles were 13.3%, 2.3%, and 42.4%, respectively, with no subjects carrying 2 defective alleles. The frequencies of the CYP2C9 *3 and VKORC1 -1639A alleles were significantly lower than those reported in different Arabian populations. None of the subjects with the VKORC1 -1639AA genotype were carriers of CYP2C9 *1/*3 genotypes that lead to sensitivity to COAs therapy. The low frequency of the CYP2C9 *3 allele combined with the absence of subjects carrying 2 defective CYP2C9 alleles suggests that, in this specific population, pharmacogenetic COAs dosing may mostly rely upon VKORC1 genotyping.
authors.affiliation: Biological Sciences Department, College of Science, King Faisal University, Hofouf 31982, Saudi Arabia.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Alzahrani
authors.forename: Georgia
authors.initials: G
authors.lastname: Ragia
authors.forename: Hamza
authors.initials: H
authors.lastname: Hanieh
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000328:Adult; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D012529:Saudi Arabia; D064417:Vitamin K Epoxide Reductases
chemical_list: D000925:Anticoagulants; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases