Genetic factors contribute to patient-specific warfarin dose for Han Chinese.
BACKGROUND
Warfarin is a commonly prescribed anticoagulant drug for the prevention of thromboses. To address the association of genetic factors and warfarin dosage for ethnic Han Chinese, we genotyped six candidate genes involved in the warfarin interactive pathway with focus on SNPs with reported association with warfarin dose.


METHODS
We recruited a study population consisted of 318 patients receiving warfarin treatment and 995 healthy controls. PCR and direct sequencing were used to identify the sequence polymorphisms.


RESULTS
In our study population, SNP rs1799853 of CYP2C9, rs1687390 of ORM1-2, and rs2069919 of PROC showed no variation. SNPs rs12714145 of GGCX and rs1799809 of PROC showed no significant correlation with warfarin dose. The associations of SNPs rs9934438 and rs9923231 of VKORC1, the 3 (rs1057910) and C(-65) (rs9332127) alleles of CYP2C9, and SNP rs4653436 of EPHXI with the dose of warfarin were significant.


CONCLUSIONS
A multiple regression model based on the genetic polymorphisms of VKORC1, CYP2C9, EPHX1 and the non-genetic factors of age and body weight can explain 40.2% of the variance in warfarin dose in Han Chinese patients. Translation of this knowledge into clinical guidelines for warfarin prescription may improve the safety and efficacy of warfarin treatment among Han Chinese.
Wang
Ting-Liang
TL
Mochtar Riady Institute for Nanotechnology, Jl. Boulevard Jend. Sudirman, No. 1688, Lippo Karawaci, Tangerang, Banten, Indonesia.
Li
Hong-Lei
HL
Tjong
Wen-Ye
WY
Chen
Qian-Su
QS
Wu
Guan-Sheng
GS
Zhu
Hai-Tao
HT
Hou
Zi-Shan
ZS
Xu
Shu
S
Ma
Sheng-Jun
SJ
Wu
Madeline
M
Tai
Susan
S
D044466:Asian People / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013379:Substrate Specificity; D013927:Thrombosis / Q000517:prevention & control; D014859:Warfarin / Q000494:pharmacology*
D014859:Warfarin