Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients.

Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Research Abstract Details 

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Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Abstract Text:

Hyun-Jung Cho,Kie-Ho Sohn,Hyang-Mi Park,Kyung-Hoon Lee,BoYoung Choi,Seonwoo Kim,June-Soo Kim,Young-Keun On,Mi-Ryung Chun,Hee-Jin Kim,Jong-Won Kim,Soo-Youn Lee,

INTRODUCTION: Warfarin, a commonly prescribed anticoagulant, exhibits large interindividual and interethnic differences in the dose required for its anticoagulation effect. Asian patients require a much lower maintenance dose compared with Caucasians; the explanation for these differences remains unknown. METHODS: We analyzed five single nucleotide polymorphisms of the vitamin K epoxide reductase complex subunit 1 gene (VKORC1) and the *3 variant of cytochrome P450 (CYP)2C9, as well as the plasma warfarin concentration, in 108 Korean patients with atrial fibrillation. RESULTS: Genotypic frequencies of VKORC1 +1173CT and CYP2C9*1/*3 were 17.6 and 10.2%, respectively, in the study population; VKORC1 +1173CC and CYP2C9*3/*4 were detected in one patient each. Patients carrying at least one copy of the VKORC1 +1173C allele, or the H7 (group B) haplotype, required a significantly higher warfarin dose (n = 20; 5.5 +/- 1.7 mg/day) than those homozygous for the +1173T allele, or the H1 (group A) haplotype, (3.8 +/- 1.2 mg/day; p < 0.001). There were statistically significant differences in warfarin dose between the CYP2C9*1/*1 (4.3 +/- 1.6 mg/day; p < 0.001) and those with the other two genotypes including CYP2C9*1/*3 and CYP2C9*3/*4 (2.7 +/- 0.9 mg/day). The multiple regression analysis revealed that the VKORC1 genotype (r2 = 0.197; p < 0.001), the age when warfarin started (r2 = 0.09; p < 0.001), body surface area (r2 = 0.041; p = 0.004) and CYP2C9 genotype (r2 = 0.029; p = 0.014) were factors associated with the daily dose of warfarin required. CONCLUSION: In the present study, we found that the VKORC1 polymorphism had a dominant genetic influence on interindividual variability for warfarin dose in Korean patients. It explained approximately 32% of the overall variability in warfarin dose requirements given all of the variables studied. Thus, analysis of the VKORC1 genotypes may be important to guide warfarin dose selection and allow personalized warfarin treatment.

Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Publishing Authors By Initials

HJ Cho,KH Sohn,HM Park,KH Lee,B Choi,S Kim,JS Kim,YK On,MR Chun,HJ Kim,JW Kim,SY Lee,

For similar heterocyclic compounds: heterocyclic compounds, 2-ring: benzopyrans: coumarins: 4-hydroxycoumarins: warfarin research abstracts see: heterocyclic compounds: heterocyclic compounds, 2-ring: benzopyrans: coumarins: 4-hydroxycoumarins: warfarin research

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Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Pharmacogenomics

VOLUME: 8

Page Numbers: 329-37

Journal Abbreviation: Pharmacogenomics

ISSN: 1744-8042

DAY: 30

MONTH: Apr

YEAR: 2007

Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Information

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LANGUAGE: eng

NlmUniqueID: 100897350

Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Keywords Mesh Terms:

KEYWORDS: Warfarin

MESH TERMS: adverse effects

Chemical & Substance for Abstract: Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients. Information

Substance Name: Cytochrome P-450 Enzyme System

Registry Number: 9035-51-2

Grant and Affiliation Information for Factors affecting the interindividual variability of warfarin dose requirement in adult Korean patients.

AFFILIATION: Sungkyunkwan University School of Medicine, Department of Laboratory Medicine, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea.

Country: England

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MEDLINETA: Pharmacogenomics

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