Factors Affecting the Interindividual Variability of Warfarin Dose Requirement in Adult Korean Patients

Cho, Hyun Jung; Sohn, KieHo; Park, Hyang-Mi; Lee, Kyung-Hoon; Choi, Byung-Min; Kim, Seonwoo; Kim, June-Soo; On, Young-Keun; Chun, Mi-Ryung; Kim, Hee‐Jin; Kim, Jong-Won; Lee, Soo-Youn

doi:10.2217/14622416.8.4.329

Cited by 55 publications

(23 citation statements)

References 37 publications

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“…The frequency of the CYP2C9 variant type was approximately 12% in other Korean studies [13,14] and was 8% in other Asians [15][16][17].…”

Section: Discussionmentioning

confidence: 81%

Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy

Kwon

et al. 2011

J Thromb Thrombolysis

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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.

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“…The frequency of the CYP2C9 variant type was approximately 12% in other Korean studies [13,14] and was 8% in other Asians [15][16][17].…”

Section: Discussionmentioning

confidence: 81%

Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy

Kwon

et al. 2011

J Thromb Thrombolysis

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“…2,4 Cho HJ et al suggested that it explained B32% of the overall variability in warfarin dose requirements given all of the variables studied in Koreans. 22 In Japanese patients, the model using the multiple regression analysis including age, sex, weight and three genetic polymorphisms accounted for 33.3% of total variations in warfarin dose. 4 Also, a multiple regression model based on the genetic polymorphisms of VKORC1, CYP2C9, EPHX1 and the non-genetic factors of age and body weight can explain 40.2% of the variance in warfarin dose in Han Chinese patients.…”

Section: Discussionmentioning

confidence: 99%

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

et al. 2011

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Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboembolic disorders. We investigated the contribution of genetic variations of four genes and clinical factors to warfarin dose requirement and provided a warfarin-dosing algorithm based on genetic and clinical variables in Korean patients. We recruited 564 Korean patients on stable anticoagulation. Single nucleotide polymorphisms (SNPs) for the VKORC1, CYP2C9, CYP4F2 and GGCX were analyzed. Using multiple regression analysis, we developed a model to predict the warfarin requirement. The SNPs of VKORC1, CYP2C9, CYP4F2 and GGCX showed significant correlation with warfarin dose. Patients with the 3730AA genotype received significantly higher doses of warfarin than those with the 3730GG (P¼0.0001). For CYP2C9, the highest maintenance dose was observed in the patients with wild-type genotype compared with the variant allele carriers (Po0.0001). The multiple regression model including age, gender, body surface area (BSA), international normalized ratio (INR) and four genetic polymorphisms accounted for 35% of total variations in warfarin dose (R 2 ¼0.3499; Po0.0001). This study shows that age, gender, BSA, INR and VKORC1, CYP2C9 and CYP4F2 polymorphism affect warfarin dose requirements in Koreans. Translation of this knowledge into clinical guidelines for warfarin prescription may contribute to improve the efficacy and safety of warfarin treatment for Korean patients.

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“…This dependent therapeutic action of the drug linked to albumin affinity has already been reported for warfarin. Although a genetic factor has been identified in 30% of cases, the other causes of variability in the therapeutic efficiency of warfarin among patients remain unknown (14)(15)(16). In the context of diabetes, hyperglycemia…”

Section: Introductionmentioning

confidence: 99%

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

Soudahome

Catan

Giraud

et al. 2018

Journal of Biological Chemistry

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Factors Affecting the Interindividual Variability of Warfarin Dose Requirement in Adult Korean Patients

Cited by 55 publications

References 37 publications

Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy

Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy

Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide

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