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Influence of clinical and genetic factors on warfarin dose requirements among Japanese patients.

Abstract：

OBJECTIVE:The aim of this study was to investigate the influence of clinical and genetic factors on warfarin dose requirements in the Japanese population. METHODS:We enrolled 125 patients on stable warfarin anticoagulant therapy with an international normalized ratio maintained between 1.5 and 3.0. PCR-based methods were performed to analyze genetic polymorphisms in the genes pharmacokinetically and pharmacodynamically related to warfarin reactions, including cytochrome P450 (CYP) 2C9, vitamin K epoxide reductase complex subunit 1 (VKORC1), gamma-glutamyl carboxylase (GGCX) and factor VII (FVII). RESULTS:The presence of CYP2C9*3 and VKORC1-1639G>A had a significant impact on the mean maintenance dose of warfarin (CYP2C9*1/*1 2.74 +/- 1.24 mg/day vs. *1/*3 and *3/*3 1.56 +/- 0.85 mg/day, P = 0.009; VKORC1-1639AA 2.42 +/- 0.95 mg/day vs. GA 3.71 +/- 1.43 mg/day vs. GG 7.25 +/- 0.35 mg/day, P < 0.001). In the multiple linear regression model, the combination of age, body surface area, and genotypes of CYP2C9*3 and VKORC1-1639G>A explained 54.8% of the variance in warfarin dose requirements. CONCLUSIONS:The influences of CYP2C9*3 and VKORC1-1639G>A on the maintenance dose of warfarin were well-defined in Japanese patients, while polymorphisms of GGCX and FVII did not affect it. The model established in this study might provide us most likely individual maintenance dose based on clinical and genetic backgrounds.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Ohno M,Yamamoto A,Ono A,Miura G,Funamoto M,Takemoto Y,Otsu K,Kouno Y,Tanabe T,Masunaga Y,Nonen S,Fujio Y,Azuma J

doi

10.1007/s00228-009-0685-9

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1097-103

issue

11

eissn

0031-6970

issn

1432-1041

journal_volume

65

pub_type

杂志文章

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