The effect of GGCX and CYP4F2 gene polymorphisms in genotype-guided dosing of warfarin in patients with a history of cardiac surgery

Abstract

Cytochrome P450 4F2 (CYP4F2) and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of warfarin, an oral anticoagulant. CYP4F2 1347 C > T and GGCX 12970 C > G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians, Chinese, Turkish and Indian populations. There are no reports about the genotype frequencies of these polymorphisms in Iranian population. In the present study, we aimed to find out the genotype frequencies of CYP4F2 1347 C > T and GGCX 12970 C > G polymorphisms and the impression on warfarin dosage in an Iranian-Azari population. CYP4F2 1347 C > T and GGCX 12970 C > G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 cases receiving warfarin after cardiac surgery. No significant differences were found between prescribed and protocol doses of warfarin based on variants of CYP4F2 1347 C > T and GGCX 12970 C > G polymorphisms. Patients with combination genotypes 1347CC/12970CG and 1347TT/12970CG demonstrated significantly different prescribed and protocol doses of warfarin. Age of patients was negatively correlated with prescribed dose of warfarin. Variations of CYP4F2 1347 C > T and GGCX 12970 C > G polymorphisms play a role in determining the required dose of warfarin in patients with cardiac surgery of Iranian-Azari population.