Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population.
OBJECTIVE
To evaluate the association of VKORC1 genetic variants with warfarin dose requirements in a Hong Kong Chinese patient population.


METHODS
A retrospective study of Hong Kong Chinese patients chronically maintained on warfarin was conducted. Single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 were genotyped. Stable warfarin dose data were retrieved from patient medical records.


RESULTS
Sixty-nine patients were included in the analysis. VKORC1 haplotypes H1 (group A) and H7 (group B) were most common, accounting for 86% and 13% of all haplotypic variation in this cohort. Patients carrying at least one copy of a VKORC1 group B haplotype (n = 16) required a significantly higher stable warfarin dose (5.17+/-1.53 mg/day) than patients that were homozygous for group A haplotypes (n = 53; 2.93+/-1.22 mg; P < 0.001). In the VKORC1 A/A group, four patients (5.8%) were heterozygous for CYP2C9*3 and had a lower dose requirement (1.94+/-0.43 mg) than patients that exhibited the CYP2C9 *1/*1 genotype (3.01+/-1.23 mg), P = 0.004. In multivariate analysis, VKORC1 and CYP2C9 explained 31% and 7.9% of the variability in warfarin dose, respectively.


CONCLUSIONS
VKORC1 genotype is the dominant genetic influence on inter-individual variability in warfarin dose in Hong Kong Chinese. The lower mean dose of warfarin in Chinese, relative to Europeans, appears to be a reflection of their preponderance of the 'low-dose' VKORC1 H1/H1 (homozygous group A) genotype.
Veenstra
David L
DL
School of Pharmacy, The Chinese University of Hong Kong, Hong Kong.
You
Joyce H S
JH
Rieder
Mark J
MJ
Farin
Federico M
FM
Wilkerson
Hui-Wen
HW
Blough
David K
DK
Cheng
Gregory
G
Rettie
Allan E
AE
D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000208:ethnology; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006331:Heart Diseases / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D006720:Homozygote; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases