The Influence of CYP4F2 Polymorphisms on Warfarin Doses in Korean Patients with a Variety of Diseases

Abstract

Purpose We sought to determine if the CYP4F2 gene could affect warfarin maintenance dosage in Korean patients with a variety of diseases. CYP4F2 was reported to affect warfarin dose, but it was controversial. Some papers showed that CYP4F2 genotype could affect warfarin stable dose to some extent. But other papers reported that CYP4F2 genotype did not affect warfarin dose. Methods We enrolled 101 patients treated with warfarin in our registry. Non-genetic factors (clinical characteristics, stable warfarin dose, INR, medication information) and CYP4F2 polymorphisms were assessed. The definition of warfarin stable dose was the amount of medication given to maintain the patient’s INR within the target range throughout at least 3 consecutive laboratory measurements separated by at least 1 week. Each patient’s target therapeutic INR range was determined by the clinicians according to the indication for warfarin treatment. Results In our study, average patient age was 64.0± 11.9 years. Females accounted for 52% of the sample. The average warfarin maintenance dose was 3.26± 1.38 (1-9) mg/day. Compared with CYP4F2 wild type patients (GG), the patients carrying a CYP4F2 heterozygous variant (GA) or a CYP4F2 homozygous variant (AA) required higher warfarin dose. The mean warfarin dose in the patients with the CYP4F2 AA genotype was 4.1± 1.9 mg/day, while that for the patients with the CYP4F2 GA genotype was 3.3± 1.3 mg/day, and that for the patients with the CYP4F2 GG genotype was 3.0± 1.2 mg/day. The difference among them was significant (P= 0.038). Conclusion CYP4F2 polymorphisms statistically influenced the stability of warfarin maintenance dosage in Korean patients with a variety of diseases. Keywords: CYP4F2 polymorphisms, Warfarin dose, Korean