The Relationship of VKORC1 and CYP2C9 Polymorphisms with Warfarin Response in Asians

Oral anticoagulants، the main drugs used for preventing coagulation، exhibit a greater than 10-fold inter-individual variability. Therefore، sometimes، conflicting responses are seen at the same dose in different people. Warfarin is an anticoagulant that is widely used، but some indivisuals show sensitivity or resistance because of pharmacogenetic events. Warfarin sensitivity is due to mutation in CYP2C9 gene. C to T change at position 430 (allele * 2)، A to C change at position 1075 (allele * 3)، and deletion of A at position 818 (* 6 allele) in this gene،cause sensitivity to warfarin with reduced enzyme activity. * 1 allele encodes a normal enzyme. Another gene is VKORC1 that encodes C1 subunit of VKOR (vitamin K epoxide reductase). It is believed that some of its polymorphisms are responsible for warfarin resistance and the others cause sensitivity to warfarin. Haplotype A containing genotypes -1639A، 1173T، 1542C، 2255C، 3730A or 3673A causes sensitivity to warfarin while 5417G>T polymorphism causes resistance to warfarin. The Asian descent carries CYP2C9 allelic variants. The allele frequency of CYP2C9 * 2 and CYP2C9 * 3 is low in Asians. CYP2C9 * 2 is especially rare in Japanese، Indo-Chinese، Indonesian and native Taiwanese people but CYP2C9 * 3 is not common in Iranian patients. The frequncy of VKORC1 A haplotype، which is associated with high warfarin sensitivity، is more than VKORC1 B haplotype، which is associated with warfarin resistance، in Asians. Because the frequency of VKORC1AA haplotype is higher in Asians، they are sensitive to warfarin.