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- Title
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.
- Authors
Gu, Qiang; Kong, Yan; Schneede, Jörn; Xiao, Ying-Bin; Chen, Lin; Zhong, Qian-Jin; Wang, Xue-Feng; Hao, Jia; Chen, Bai-Cheng; Chen, Jing-Jin
- 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 of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.
- Subjects
CHINA; DRUG therapy; AGE distribution; ANALYSIS of variance; BLOOD coagulation tests; BODY weight; CHI-squared test; COMPUTER software; FISHER exact test; GENES; GENETIC polymorphisms; PROSTHETIC heart valves; HEME; LIQUID chromatography; MILITARY hospitals; MULTIVARIATE analysis; PHARMACEUTICAL arithmetic; POLYMERASE chain reaction; RESEARCH funding; STATISTICS; T-test (Statistics); U-statistics; VITAMIN K; WARFARIN; DATA analysis; MULTIPLE regression analysis; BODY mass index; DRUG administration; DRUG dosage
- Publication
European Journal of Clinical Pharmacology, 2010, Vol 66, Issue 12, p1217
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-010-0863-9