Warfarin dose requirements with different genotypes of CYP2C9 and VKORC1 for patients with atrial fibrillation and valve replacement.
To investigate whether genetic variants ofCYP2C9andVKORC1have different effects on the dose of warfarin in 180 Han Chinese patients who were recruited from the Fu Wai Hospital. All were on maintenance treatment with stable daily warfarin doses for a period of at least 3 months.



DNA was isolated and genotyped using a Warfarin dosage Prediction Kit for single nucleotide polymorphisms (SNPs) ofCYP2C9andVKORC1.



TheVKORC1andCYP2C9*3polymorphisms are significantly associated with warfarin maintenance dosages. Patients with AG&GG genotype inVKORC1needed higher doses than those with AA genotypes (4.55 ± 1.27 mg/ day vs. 2.90 ± 0.97 mg/day, p < 0.001). Patients with *1/*3 genotype inCYP2C9need doses lower than those with *1/*1 genotypes (1.73 ± 0.95 mg/day vs. 3.23 ± 1.13 mg/day, p < 0.001). There were no significant differences between the warfarin maintenance dosages in patients with atrial fibrillation (3.09 ± 1.16 mg/day), patients with heart valve replacement (2.95 ± 1.21 mg/day) and those with both atrial fibrillation and heart valve replacement (3.36 ± 1.13 mg/day) (p > 0.05). The mean warfarin daily dose requirements in the genotypes ofVKORC1andCYP2C9were not dependent on the medical indication(s) present.



Genetic variants ofCYP2C9, VKORC1, and age are significant determinants of the maintenance dose of warfarin. The medical indications atrial fibrillation, valve replacement, or a combination of both are not determinants of the warfarin dose requirements.
Weirong
W
Chen
Luhua
L
Wu
Xin
X
Liu
Yue
Y
Shen
Yan
Y
Liang
Jun
J
Zhu
Huiqiong
H
Tan
Yanmin
Y
Yang
Qun
Q
Liu
Mingsheng
M
Wang
Lisheng
L
Liu
Xingyu
X
Wang
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001021:Aortic Valve / Q000601:surgery*; D001777:Blood Coagulation / Q000187:drug effects; D002681:China; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D054796:Drug Dosage Calculations; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects*; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013927:Thrombosis / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000235:genetics* / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases