Dependency of phenprocoumon dosage on polymorphisms in the VKORC1 and CYP2C9 genes.
OBJECTIVE
Polymorphisms in the vitamin K epoxide-reductase-complex-1 (VKORC1) and the cytochrome-P450-isozyme (CYP2C9) genes account for therapeutic responses to vitamin K antagonists (VKA). This study aimed to investigate the prevalence of VKORC1 and CYP2C9 polymorphisms among patients under phenprocoumon and its influence on the VKA dosage.


METHODS
Patients under phenprocoumon were screened for the polymorphisms -1639G > A and 3730G > A in the VKORC1 gene and 430C > T and 1075A > C in the CYP2C9 gene by means of a StripAssay. Baseline clinical and laboratory parameters were registered.


RESULTS
Among 53 patients (28 females, mean age 72.5 years), VKORC1 polymorphisms were found in 34 [-1639G > A: homozygote (n = 11), heterozygote (n = 23)] and 28 [3730G > A: homozygote (n = 7), heterozygote (n = 21)] patients. Thirteen patients were compound heterozygote. CYP2C9 polymorphisms were found in 12 [430G > T: homozygote (n = 1), heterozygote (n = 11)] and 7 [1075A > C: homozygote (n = 0), heterozygote (n = 7)] patients. Seventeen patients had at least one VKORC1 and one CYP2C9 polymorphism. Mean phenprocoumon dosage per week to achieve therapeutic anticoagulation was lower (higher) in patients with than without the VKORC1 polymorphism -1639G > A (3730G > A) or the CYP2C9 polymorphisms. Despite the presence of VKORC1 or CYP2C9 polymorphisms, mean International Normalized Ratio was not significantly different between patients with and without polymorphisms.


CONCLUSIONS
Though VKORC1 and CYP2C9 polymorphisms influence the phenprocoumon dosage necessary to achieve therapeutic anticoagulation, anticoagulation is therapeutic if carefully monitored.
Qazim
Berisha
B
Second Medical Department, Krankenanstalt Rudolfstiftung, Vienna, Austria.
Stöllberger
Claudia
C
Krugluger
Walter
W
Dossenbach-Glaninger
Astrid
A
Finsterer
Josef
J
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003430:Cross-Sectional Studies; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010644:Phenprocoumon / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases
D000925:Anticoagulants; 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; D010644:Phenprocoumon