Coumarin derivatives such as
warfarin and
acenocoumarol are used in various disorders such as
deep venous thrombosis,
pulmonary embolism,
atrial fibrillation and
artificial heart valves. They have improved prognosis of patients with thromboembolic disease. An individual's response to
coumarins depends on several factors. The non-genetic factors include age, gender, body mass index, diet and interacting drugs. Among the genetic factors, the
cytochrome P450 system and
vitamin K epoxide reductase complex subunit 1 play a key role in drug metabolism. This was a prospective hospital based study in which allele and genotypic frequencies of
CYP2C9 gene polymorphisms; 430C>T and 1075A>C and VKORC1 gene polymorphisms; 1639G>A, 9041G>A and 6009C>T in 106 alleles of north Indian patients with valve replacement on
acenocoumarol were determined and their effect on
acenocoumarol dosing was studied. To the best of our knowledge, this is first report of VKORC1 9041G>A and 6009C>T gene polymorphisms and their effect on
acenocoumarol dosing from north India. In 53 patients with valve replacement on
acenocoumarol with stable INR, the allele frequency of
CYP2C9*2 and
CYP2C9*3 gene polymorphisms was 0.05 and 0.17 respectively and that of VKORC1 *2,*3 and *4 gene polymorphisms was 0.15, 0.72 and 0.11 respectively. The presence of
CYP2C9*3 or VKORC1*2 gene polymorphism were associated with decrease in
acenocoumarol dose requirements (p values 0.03 and 0.02 respectively).This study confirmed the association of lower mean weekly dosages of
acenocoumarol in patients with
CYP2C9*3 and VKORC1*2 gene polymorphisms. An unusually high frequency of 9041A polymorphism in VKORC1 was found in study population.