Association of genetic polymorphisms with warfarin dose requirements in Chinese patients.
OBJECTIVE
Warfarin is a commonly used anticoagulant with a narrow therapeutic range and large interindividual differences in dosing requirements. Previously, studies have identified that the interindividual variability was influenced by varieties of factors, including age, body size, vitamin K intake, interacting medications, as well as genetic variants. We aimed to investigate the effect of single-nucleotide polymorphisms (SNPs) on the interindividual variability of warfarin dose requirements in Chinese patients.


METHODS
The study population consisted of 300 patients with a stable maintenance dose of warfarin. We examined SNPs in eight genes involving in the biotransformation and mode of action of warfarin (i.e., CYP4F2, CYP2C19, APOE, CALU, EPHX1, PROC, CYP2C9, and GGCX) using the SNaPshot assay.


RESULTS
The mean daily warfarin dose in patients carrying CYP2C19 rs3814637CC, CYP2C9 rs1057910AA, and GGCX rs699664AA genotype was 3.39, 3.34, and 3.51 mg/day, respectively, which was higher than those carrying CYP2C19 rs3814637TT, CYP2C9 rs1057910CC, and rs699664GG genotype (2.00, 0.81, and 3.09 mg/day, respectively).


CONCLUSIONS
These findings indicate that individuals carrying the CYP2C19 rs3814637CC or CYP2C9 rs1057910AA or GGCX rs699664AA genotype needed higher warfarin doses in the Chinese population.
1 School of Forensic Medicine, Kunming Medical University , Kunming, People's Republic of China .
Yundan
Y
Liang
Zhiyu
Z
Chen
Gang
G
Guo
Xuemei
X
Dong
Chunting
C
Wu
He
H
Li
Tong
T
Wang
Bingying
B
Xu
D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D002681:China; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19