Study of the Association of Warfarin Dosage and Plasma Enantiomer Concentration With the Gene Polymorphisms of CYP and VKOR

Oral warfarin anticogulation for the prevention and treatment of patients with venous thromboembolism is one of the most used therapies in clinical practice. Patients require different dosage to achieve the target therapeutic anticoagulation. Optimal dosage and bleeding complication are two most clinical concerns. Besides of multiple individual factors (e.g. age, dietary intake, vitamin supplement, drug compliance etc.), some genetic factors may determine the drug requirement and safety.

The cytochrome P450 CYP2C9 is a liver enzyme required for the oxidative metabolism of warfarin. The vitamin K epoxide redutase (VKOR) is a liver enzyme associated with the reuse of the oxidative hydroquinone form of vitamin K. The VKOR enzyme is the target of warfarin. Recent studies revealed both genes may determine the pharmacodynamic of warfarin anticogualation. To date, there are more than thirteen identified polymorphism at CYP2C9 gene. Majority of those variant polymorphisms may decrease the warfarin requirement. The VKOR complex subunit 1 (VKORC1) is a newly identified gene. Some polymorphisms also were reported.

As we know, the Chinese patients need a lower dosage of warfarin in comparison with the Caucasian patients. We are interested in finding the genetic causes of Taiwneses Chinese patients. In our study we will first identify the polymorphism patterns of these two genes in normal population. Then, we will try to find the association between these polymorphism and patient warfarin requirement. Our pharmacogenetics study will be valuable for prevention of bleeding complication of warfarin treatment in Chinese population.