The Impact of "CYP2C9" and "VKORC1" Genetic Polymorphism upon Oral Anticoagulation Requirements

Background: Polymorphisms in the gene encoding the cytochrome P-450 2C9 enzyme (CYP2C9) are known to contribute to variability in sensitivity to Marevan. CYP2C9 is the enzyme primarily responsible for the metabolic clearance of s-enantiomer of Marevan. The VKORC1 is the target of Coumarin anticoagulants, and its common genetic variants result in altered sensitivity to Marevan. VKORC1 polymorphisms are associated with a need for lower doses of Marevan during long-term therapy.
Aim of work:This study aimed to assess the allelic frequencies and to investigate the relationship between "CYP2C9" and "VKORC1" genotype and vitamin K antagonist anticoagulation.
Subjects and Methods: This study was conducted on 40 patients. They were 24 females and 16 males with a male to female ratio 2:3. Their ages ranged from 28 to 72 years old. All the studied subjects were laboratory investigated with international normalized ratio (INR), complete blood count (CBC) and detection of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) by polymerase chain reaction (P.C.R.) reverse hybridization method using PGX thrombo strip assay (Vienna Lab., Austria).
Results: Regarding the distribution of patients according to frequency of deep venous thrombosis (DVT) attacks, 16 (40%) patients showed single attack of DVT and 24 (60%) patients showed recurrent attacks. Patients with single attack of DVT were 12 (75%) females and 4 (25%) males with male to female ratio of 1:3. As for patients with recurrent attacks of DVT, they 13 (54.2%) females and 11(45.8%) males with a male to female ratio of 1:1.2.
Conclusion: Detection of genetic polymorphisms in CYP2C9 and VKORC1 genes prior to onset of warfarin therapy, greatly influenced response to warfarin and shortened the time required to reach target INR, and hence reduced the risk of recurrence of deep venous thrombosis.