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

  • Pharmacogenetics
  • Published:
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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.

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Compliance with ethical standards

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Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

All procedures performed in this study involving participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki Declaration and its later amendments (IRB No. 2009-4-0283).

Informed consent

Informed consent was obtained from all individual participants included in this study.

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Authors and Affiliations

  1. College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayedae-gil, Seodaemun-gu, Seoul, 120-750, South Korea

    Jee-Eun Chung, Kyung Eun Lee, Joo Hee Kim & Hye Sun Gwak

  2. Department of Thoracic & Cardiovascular Surgery, Yonsei University Medical Center, Seoul, 120-752, South Korea

    Byung Chul Chang

  3. College of Pharmacy, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk, 361-763, South Korea

    Kyung Eun Lee

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  1. Jee-Eun Chung
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Correspondence to Hye Sun Gwak.

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Chung, JE., Chang, B.C., Lee, K.E. et al. Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves. Eur J Clin Pharmacol 71, 1229–1236 (2015). https://doi.org/10.1007/s00228-015-1915-y

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  • DOI: https://doi.org/10.1007/s00228-015-1915-y

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