VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients.
OBJECTIVE
The objective of this study was to determine the quantitative influence of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP 2C9) polymorphisms on warfarin dose requirements in Turkish patients.


METHODS
A total of 205 patients taking warfarin for >2 months were enrolled in the study. Deoxyribonucleic acid (DNA) samples from these patients were genotyped for polymorphisms in VKORC1 and CYP2C9 genes. A linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on mean warfarin dose requirements.


RESULTS
The VKORC1 promoter polymorphism (3673 G>A) was associated with differences in weekly mean varfarin dose: for GG genotype the dose was 43.18 mg/week, for GA genotype 33.78 mg/week and for AA genoype 25.83 mg/week (P < 0.0001). Patients who carried VKORC1 and CYP2C9 variants needed a 40% lower mean weekly warfarin dose compared to wild types. Variables associated with lower warfarin dose requirements were VKORC1 3673 AA or GA genotype (both P < 0.0001), one or two CYP2C9 variant alleles (both P < 0.0001), increasing age (P < 0.0001) and non-indication of venous thromboembolism for warfarin therapy (P = 0.002).


CONCLUSIONS
Polymorphisms in VKORC1 and CYP2C9 genes were important determinants of warfarin dose requirements in Turkish patients.
University of Istanbul, Istanbul, Turkey.
G
G
Oner Ozgon
T Y
TY
Langaee
H
H
Feng
N
N
Buyru
T
T
Ulutin
A C
AC
Hatemi
A
A
Siva
S
S
Saip
J A
JA
Johnson
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic; D014421:Turkey; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use
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