title: Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy.
abstract: During warfarin treatment, determining the optimal dose and maintaining the target PT-INR are challenging. Increasing evidence supports the theory that genotypic polymorphisms influence an individual's warfarin dose requirement. In this study, we evaluated allele frequencies and effects of CYP2C9 and VKORC1 on warfarin response during initial anticoagulation therapy in Korean patients. We enrolled patients who had initiated warfarin therapy and undergone PT-INR testing at least three times within the first month of anticoagulation therapy. All the participating patients were tested for the detection of CYP2C9*3 (c.1075A>C) and VKORC1-1639G>A. A melting-curve analysis after real-time PCR was performed using CYP2C9*3 and VK1639 genotyping kits (Idaho Technology, US). A total of 37 patients were enrolled in this study. CYP2C9*1/*1 (87%) and VKORC1-1639AA genotypes (89%) were predominant in Korea. The CYP2C9*3 and VKORC1-1639G alleles were found in five (13%) and four patients (11%), respectively. Patients with the CYP2C9*3 allele received a lower warfarin dose (P = 0.018) and tended to show more rapid PT-INR increase than CYP2C9*1/*1 genotype. Patients with the VKORC1-1639G allele nonsignificantly received higher warfarin dose than those without. The CYP2C9*3 and VKORC1-1639G alleles influenced warfarin response during the first month of anticoagulation therapy. Considering these results, CYP2C9 and VKORC1 genotyping can be an useful tool to estimate initial warfarin dose and frequency of PT-INR monitoring during the first month of anticoagulation therapy.
authors.affiliation: Department of Laboratory Medicine, Hallym University College of Medicine & Hallym University Sacred Heart Hospital, 896 Pyeongchon-dong, Dongan-gu, Anyang, Gyeonggi-do, Seoul 431-070, Korea.
authors.forename: Aerin
authors.initials: A
authors.lastname: Kwon
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Jo
authors.forename: Hyoung-June
authors.initials: HJ
authors.lastname: Im
authors.forename: Yun-A
authors.initials: YA
authors.lastname: Jo
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Hyoun Chan
authors.initials: HC
authors.lastname: Cho
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D007723:Korea; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases