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1. Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Oct;39(10):929-35.

[Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation
of therapy].

[Article in Chinese]

Liu Y, Zhong SL, Tan HH, Yang M, Fei HW, Yu XY, Lin SG.

Guangdong cardiovascular institute, Guangdong general hospital, Guangdong Academy
of Medical Sciences, Guangzhou 510080, China.

OBJECTIVE: To investigate potential contributions of genetic variants of
cytochrome P-450 2C9 (CYP2C9) and vitamin K expoxide reductase (VKORC1) to the
anticoagulation response during the initiation of warfarin therapy in the Han
Chinese population.
METHODS: A total of 798 Han Chinese patients received long-term warfarin
anticoagulant therapy orally after valve replacement in our hospital between 2000
and 2008 were included in this study. Nine single nucleotide polymorphism (SNP)
loci [rs12572351 G > A, rs9332146 G > A, rs4917639 G > T, rs1057910 A > C
(CYP2C9(*)3), rs1934967 G > T, rs1934968 G > A, rs9923231 C > T (VKORC1-1639 G >
A), rs2359612 G > A and rs10871454 C > T] in 2 genes including CYP2C9 and VKORC1,
which were possibly correlated with warfarin pharmacokinetics and
pharmacodynamics through literature retrieval, were selected and analyzed.
Warfarin steady-state dose requirement, time to the INR (the international
normalized ratio) within the therapeutic range and percent of the INR of more
than 3.5 were compared among genotype subgroups. SNaPshot technique was used to
detect gene SNPs; Hardy-Weinberg genetic equilibrium test was used to test
population representativeness.
RESULTS: CYP2C9(*)3 genotype did not affect the required warfarin dose while it
was associated with increased risk of bleeding when treated with routine dosage
regimen during the initiation of treatment. The allelic mutation frequency at
VKORC1 gene rs10871454G > A and VKORC1-1639G > A SNP loci was 92.04% and 88.03%,
respectively and rs10871454 was in perfect linkage disequilibrium with-1639.
Patients with VKORC1 rs10871454 genetic mutation required lower warfarin dose in
the first 28 days of therapy. VKORC1-1639 genetic polymorphism was also
associated with shorter time to the INR within the therapeutic range and
increased risk of over-anticoagulation.
CONCLUSION: Detecting genetic polymorphism of CYP2C9 and VKORC1 could guide
clinical use of warfarin to reduce the risk of adverse reactions including
bleeding in patients receiving chronic anticoagulation therapy.

PMID: 22321278 [PubMed - in process]