CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects

K. Nakamura, K. Obayashi, T. Araki, T. Aomori, Y. Fujita, Y. Okada, M. Kurabayashi, A. Hasegawa, S. Ohmori, T. Nakamura, K. Yamamoto

研究成果: Article

23 引用 (Scopus)

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What is known and Objective: Polymorphisms in the gene encoding CYP4F2 may partly explain the variability in warfarin maintenance dose by altering the metabolism of vitamin K. To determine the genetic factors that cause large inter-patient variability in warfarin efficacy, we investigated the relationship between serum warfarin concentration and CYP4F2 V433M (1347C>T, rs2108622) polymorphism in Japanese subjects. Methods: Gene variations in VKORC1, CYP2C9 and CYP4F2 were analysed in 126 Japanese patients treated with warfarin. The daily dosage of warfarin, concentration of S- and R-warfarin in plasma, and prothrombin time international normalized ratio (PT-INR) was used as the pharmacokinetic and pharmacodynamic indices. Results and Discussion: The maintenance dose of warfarin was larger in the CYP4F2 1347 CT genotype group (3·59 ± 1·80 mg/day, P = 0·027) than in the CYP4F2 CC genotype group (2·88 ± 1·00 mg/day). CYP4F2 1347C>T polymorphism significantly affected serum R-warfarin concentration when the VKORC1-1639 genotypes are AG and GG. What is new and Conclusion: Although a significant inter-patient difference in warfarin maintenance dose was observed between the CYP4F2 CC and CT genotypes, serum S-warfarin concentration was not significantly different between them. An effect of CYP4F2 V433M polymorphism on warfarin maintenance dose was observed but was relatively small when compared to the effects of CYP2C9 and VKOR polymorphism.

元の言語English
ページ(範囲)481-485
ページ数5
ジャーナルJournal of Clinical Pharmacy and Therapeutics
37
発行部数4
DOI
出版物ステータスPublished - 2012 8 1
外部発表Yes

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

これを引用

Nakamura, K., Obayashi, K., Araki, T., Aomori, T., Fujita, Y., Okada, Y., Kurabayashi, M., Hasegawa, A., Ohmori, S., Nakamura, T., & Yamamoto, K. (2012). CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. Journal of Clinical Pharmacy and Therapeutics, 37(4), 481-485. https://doi.org/10.1111/j.1365-2710.2011.01317.x