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Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves

Title
Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves
Authors
Chung, Jee-EunChang, Byung ChulLee, Kyung EunKim, Joo HeeGwak, Hye Sun
Ewha Authors
곽혜선김주희
SCOPUS Author ID
곽혜선scopus; 김주희scopus
Issue Date
2015
Journal Title
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
ISSN
0031-6970JCR Link1432-1041JCR Link
Citation
vol. 71, no. 10, pp. 1229 - 1236
Keywords
NAD(P)H quinone oxidoreductase 1Single nucleotide polymorphismVKORC1Warfarin
Publisher
SPRINGER HEIDELBERG
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Purpose NAD(P)H dehydrogenase, encoded by NAD(P)H quinone oxidoreductase 1 (NQO1), is an enzyme that catalyzes the reduction of quinones, including vitamin K. Given its potential role in vitamin K metabolism, this study aimed to investigate the effects of NQO1 polymorphisms on stable warfarin doses. Methods We tested a possible effect of gene polymorphisms on variability in warfarin response using 206 Korean patients with mechanical cardiac valves. Single nucleotide polymorphisms (SNPs) of NQO1 with a minor allele frequency of at least 15 % were included. Also, genotypes of vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 (CYP) 2C9, CYP4F2, gamma-glutamyl carboxylase (GGCX), and GATA4 were determined. Results NQO1 rs1800566 (C > T) and rs10517 (C > T) were significantly associated with stable warfarin doses. Variant homozygote carriers required lower stable warfarin doses than those with wild-type C allele in rs1800566 (4.85 +/- A 1.61 vs. 5.61 +/- A 1.94 mg; p = 0.033), whereas patients with wild homozygote required lower doses than those with T allele in rs10517 (5.11 +/- A 1.73 vs. 5.75 +/- A 1.98 mg; p = 0.017). Similar results were obtained from stratified analysis using VKORC1 variant homozygote carriers in both SNPs. Multivariate analysis showed that rs10517 (C > T) increased contribution of gene variations to the overall warfarin dose variability from 42.5 to 43.8 %. Conclusions Our results demonstrate that NQO1 gene polymorphisms influence stable warfarin doses in Korean patients.
DOI
10.1007/s00228-015-1915-y
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약학대학 > 약학과 > Journal papers
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