Effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement in Central China Han populations

Zhi-Jiang Li Li,Xu Liu

doi:10.4314/tjpr.v17i11.23

Abstract

Purpose: To investigate the frequency of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) and determine the effect of these genetic factors on weekly warfarin dose requirement in Central China Han populations.Methods: A total of 333 hospitalized patients with deep venous thrombosis after minimally invasive surgery were enrolled in this study. Genotypes of VKORC1 and CYP2C9 were analyzed by polymerase chain reaction (PCR)-DNA Chip method. Multiple linear regression analysis was used to explore the impact on weekly warfarin dose requirement.Results: The allele frequencies of VKORC1 -1639 G and VKORC1 -1639 A were 0.105 and 0.895, respectively, whereas no genotype of CYP2C9*1*2, CYP2C9*2*2 and CYP2C9*3*3 were found, and the allele frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 were 0.943, 0.015 and 0.042, respectively. Multiple linear regression analysis indicated that several factors including VKORC1 -1639 G>A, CYP2C9*2, CYP2C9*3, age, body mass index (BMI) and amiodarone use may explain the 47.2 % of individual variations in the weekly warfarin doses requirement.Conclusion: There is no significant difference in the frequency of VKORC1 (-1639 G>A), CYP2C9*2 and CYP2C9*3 compared to those of Asian populations, but there is significant difference when compared with those of Europeans and Caucasians. Considering VKORC1 -1639 G>A, CYP2C9*2, and CYP2C9*3 genetic polymorphisms as well as age, BMI and amiodarone use may explain the 47.2% of individual variations in the weekly warfarin doses requirement..Keywords: Warfarin, CYP2C9, VKORC1, Polymorphism, Body mass index, International normalized ratio

Highlights

Warfarin, a vitamin K antagonist, is a highly effective and commonly oral anticoagulation therapy, but it has a narrow therapeutic index.Under-anticoagulation or over-anticoagulation increased the risk of thrombosis and bleeding, respectively [1]
The FDA requires manufacturers to revise the warfarin label based on genetic polymorphisms in vitamin K epoxide reductase subunit C1 (VKORC1) and CYP2C9 in January 2010 [4]
Our data indicated that several factors including VKORC1 -1639 G/A, CYP2C9*2, CYP2C9*3, age, body mass index (BMI) and amiodarone use could explain 47.2% of individual variations in warfarin doses

Summary

Introduction

A vitamin K antagonist, is a highly effective and commonly oral anticoagulation therapy, but it has a narrow therapeutic index. Under-anticoagulation or over-anticoagulation increased the risk of thrombosis and bleeding, respectively [1]. The international normalized ratio (INR) plays an important role in the efficacy and safety of warfarin treatment, dosage adjustments are often necessary [2]. The variability in warfarin therapy is a multifactorial issue. Genetic variation play important roles in the warfarin response [3]. The FDA requires manufacturers to revise the warfarin label based on genetic polymorphisms in vitamin K epoxide reductase subunit C1 (VKORC1) and CYP2C9 in January 2010 [4]

Objectives

Methods

Results

Discussion

Conclusion