Investigation of the Effects of Genetic Variations in CYP۲C۹ and VKORC۱ on Warfarin Dose Requirements Among Iranian Patients from Khorramabad, Lorestan Province, West of Iran

Background: 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 CYP۲C۹ and VKORC۱ genes significantly influence warfarin dose requirements. This study aimed to examine the impact of various genotypes on warfarin dose requirements among Iranian patients. Methods: Blood samples were collected from ۱۱۷ 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. Results: Among the ۱۱۷ patients, no significant differences were observed in the mean daily warfarin dose requirement among the genotypes of the CYP۲C۹۳ (۱۰۷۵A>C) polymorphism. However, significant differences were found among the genotypes of CYP۲C۹۲ (۴۳۰C>T). Furthermore, the mean daily warfarin dose requirements varied significantly among the wild-type, heterozygous, and mutant genotypes for two VKORC۱ polymorphisms: VKORC۱ (۱۱۷۳C>T) and VKORC۱ (۱۶۳۹G>A). Conclusion: Our findings demonstrate that CYP۲C۹ and VKORC۱ 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.

کلیدواژه ها:

CYP۲C۹ ، genetic variations ، VKORC۱ ، warfarin