Masoumeh Dehghan Manshadi - National Institue of Genetic Engineering and Biotechnology
Omid Aryani - Iran University Medical Science Department of Neuroscience Tehran,Iran
Vadieh Ghodsinejad - National Institue of Genetic Engineering and Biotechnology
Arash Kadivari - National Institue of Genetic Engineering and Biotechnology

Warfarin (Coumadin) is the most commonly used vitamin K antagonist. It has demonstrated effectiveness for the primary and secondary prevention of venous thromboembolism, for the prevention of systemic embolism in patients with prosthetic heart valves or atrial fibrillation, as an adjunct in the prophylaxis of systemic embolism after myocardial infarction, and for reducing the risk of recurrent myocardial infarction.Warfarin is metabolized primarily via oxidation in the liver by CYP2C9, and exerts its anticoagulant effect by inhibiting the protein vitamin K epoxide reductase complex, subunit 1 (VKORC1). Three single nucleotide polymorphisms (SNPs), two in the CYP2C9 gene and one in the VKORC1 gene, have been found to play key roles in determining the effect of warfarin therapy on coagulation.This study investigates the impact of these polymorphisms on 50 patients, referred to our Laboratory for determining the appropriate dose of warfarin. After DNA extraction of whole blood , PCR reverse dot blots technique was used to determine the polymorphism of CYP2C9 gene and VKORC1 gened in collected DNA samples. VKORC1 G/A was the most common genotype of VKORC1 allele among the study samples,with a rate of 56.2%. In CYP2C9 variant, 22% and 13.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively.The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects.

CYP2C9 and VKORC1 polymorphisms, Polymerase Change Reaction, Warfarin dose requirements