VKORC1 Gene Analysis of Some Iranian Sensitive Patients to Warfarin
VKORC1 is a component of the enzyme that is the therapeutic target site of warfarin. In order to investigate the relationship between VKORC1 gene and warfarin dose response, we studied this gene in 22 clinically sensitive patients and 36 clinically normal patients as control group that in previous studies their blood warfarin levels were determined by HPLC and genotyped for CYP2C9. In the majority of these patients, the results had shown that the clinical phenotype was according to the CYP2C9 genotype, but there were sensitive patients with normal CYP2C9 genotype. So in this study for investigation of another reason of sensitivity to warfarin in these patients, VKORC1 was chosen. In order to determine the impact of VKORC1 1173C>T and 3730G>A polymorphisms in warfarin dose variability, a protocol of RFLP based PCR with HinfI and SsiI was used. Polymorphisms of VKORC1 were effective factors in sensitivity to warfarin in the majority of them. However, in some of sensitive patients, there was inconformity of clinical phenotypes with CYP2C9 and VKORC1 genotypes. In conclusion, our findings suggest that CYP2C9 and VKORC1 are not the only effective factors in sensitivity to warfarin and more studies are necessary for investigation of sensitivity reasons in these patients.
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