title: Effects of NAD(P)H quinone oxidoreductase 1 polymorphisms on stable warfarin doses in Korean patients with mechanical cardiac valves.
abstract: OBJECTIVE
  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%.
  
  
  CONCLUSIONS
  Our results demonstrate that NQO1 gene polymorphisms influence stable warfarin doses in Korean patients.
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayedae-gil, Seodaemun-gu, Seoul, 120-750, South Korea.
authors.forename: Jee-Eun
authors.initials: JE
authors.lastname: Chung
authors.affiliation: Department of Thoracic & Cardiovascular Surgery, Yonsei University Medical Center, Seoul, 120-752, South Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Chang
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayedae-gil, Seodaemun-gu, Seoul, 120-750, South Korea.|College of Pharmacy, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, Chungbuk, 361-763, South Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayedae-gil, Seodaemun-gu, Seoul, 120-750, South Korea.
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayedae-gil, Seodaemun-gu, Seoul, 120-750, South Korea. hsgwak@ewha.ac.kr.
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Gwak
mesh_terms: D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D004150:Dipeptidases / Q000235:genetics; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D012737:Sex Factors; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D004150:Dipeptidases; C034353:gamma-glutamyl dipeptidase
keywords: NAD(P)H quinone oxidoreductase 1; Single nucleotide polymorphism; VKORC1; Warfarin