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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
Authors
Chung, Jee-EunLee, Kyung EunChang, Byung ChulGwak, Hye Sun
Ewha Authors
곽혜선
SCOPUS Author ID
곽혜선scopus
Issue Date
2018
Journal Title
GENE
ISSN
0378-1119JCR Link1879-0038JCR Link
Citation
vol. 641, pp. 68 - 73
Keywords
Epoxide hydrolase 1VKORC1L1Vitamin K cycleGenetic polymorphismStable warfarin dosesNumber needed to genotype
Publisher
ELSEVIER SCIENCE BV
Indexed
SCI; SCIE; SCOPUS WOS scopus
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.
DOI
10.1016/j.gene.2017.10.049
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약학대학 > 약학과 > Journal papers
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