VKORC1-1639G>A, CYP2C9, EPHX1691A>G Genotype, Body Weight, and Age Are Important Predictors for Warfarin Maintenance Doses in Patients with Mechanical Heart Valve Prostheses in Southwest China

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 2010 Sep 16

PMID 20842355

Citations 23

Authors

Qiang Gu

Yan Kong

Jorn Schneede

Ying-Bin Xiao

Lin Chen

Qian-Jin Zhong

Xue-Feng Wang

Jia Hao

Bai-Cheng Chen

Jing-Jin Chen

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the contribution of genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 gene VKORC1-1639G>A, cytochrome P450 2C9 gene (CYP2C9), EPHXI, and clinical factors to warfarin sensitivity in southwest Chinese Han patients with mechanical heart valve prostheses.

Methods: A total of 127 patients with mechanical heart valve prostheses who have been followed up at our department during the past 23 years were enrolled in this study and compared to a control group that consisted of 133 randomly selected healthy blood donors. These Chinese patients met stable warfarin dosage requirements and had reached the target international normalized ratio (INR) of 1.5-2.0. PCR and direct sequencing were carried out to identify the polymorphisms of VKORC1-1639G>A (rs9923231), CYP2C9*3 (rs1057910), CYP2C9 IVS3-65G>C (rs9332127), and EPHX1691A>G (rs4653436). In addition, total and free (non-protein-bound) warfarin concentrations were analyzed.

Results And Conclusions: There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.

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