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Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses

Title
Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses
Author
정지은
Keywords
Epoxide hydrolase 1; VKORC1L1; Vitamin K cycle; Genetic polymorphism; Stable warfarin doses; Number needed to genotype
Issue Date
2018-01
Publisher
ELSEVIER SCIENCE BV
Citation
GENE, v. 641, Page. 68-73
Abstract
The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A > G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02 +/- 1.56 vs. 5.96 +/- 2.01 mg; p = 0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses.
URI
https://www.sciencedirect.com/science/article/pii/S0378111917308958http://repository.hanyang.ac.kr/handle/20.500.11754/80892
ISSN
0378-1119
DOI
10.1016/j.gene.2017.10.049
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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