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

Jee Eun Chung, Byung Chul Chang, Kyung Eun Lee, Joo Hee Kim, Hye Sun Gwak

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11 Scopus citations

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 ± 1.61 vs. 5.61 ± 1.94 mg; p = 0.033), whereas patients with wild homozygote required lower doses than those with T allele in rs10517 (5.11 ± 1.73 vs. 5.75 ± 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 %. Conclusion: Our results demonstrate that NQO1 gene polymorphisms influence stable warfarin doses in Korean patients.

Original languageEnglish
Pages (from-to)1229-1236
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume71
Issue number10
DOIs
StatePublished - 13 Oct 2015

Keywords

  • NAD(P)H quinone oxidoreductase 1
  • Single nucleotide polymorphism
  • VKORC1
  • Warfarin

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