Investigation of the Effects of Genetic Variations in CYP2C9 and VKORC1 on Warfarin Dose Requirements Among Iranian Patients from Khorramabad, Lorestan Province, West of Iran

Warfarin, a commonly prescribed anticoagulant with a narrow therapeutic index, poses challenges in determining the appropriate dosage due to genetic variations among individuals. Incorrect dosing of warfarin can lead to catastrophic adverse events. Observational studies have shown that single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes significantly influence warfarin dose requirements. This study aimed to examine the impact of various genotypes on warfarin dose requirements among Iranian patients.

Blood samples were collected from 117 patients and stored in tubes containing EDTA. DNA was extracted, and the different alleles and genotypes of the studied SNPs were identified using the PCR-RFLP technique.

Among the 117 patients, no significant differences were observed in the mean daily warfarin dose requirement among the genotypes of the CYP2C93 (1075A>C) polymorphism. However, significant differences were found among the genotypes of CYP2C92 (430C>T). Furthermore, the mean daily warfarin dose requirements varied significantly among the wild-type, heterozygous, and mutant genotypes for two VKORC1 polymorphisms: VKORC1 (1173C>T) and VKORC1 (1639G>A).

Our findings demonstrate that CYP2C9 and VKORC1 polymorphisms significantly affect warfarin maintenance dose requirements in Iranian patients. This information can improve the prediction of appropriate warfarin dosages and reduce the risk of over-anticoagulation or under-anticoagulation.