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

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)481-485
Number of pages5
JournalJournal of Clinical Pharmacy and Therapeutics
Volume37
Issue number4
DOIs
Publication statusPublished - 2012 Aug
Externally publishedYes

Fingerprint

Warfarin
Genes
Genotype
Serum
International Normalized Ratio
Vitamin K
Prothrombin Time
Pharmacokinetics

Keywords

  • CYP4F2
  • oxide
  • polymorphism
  • reductase
  • vitamin K
  • warfarin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. / Nakamura, K.; Obayashi, K.; Araki, T.; Aomori, Tohru; Fujita, Y.; Okada, Y.; Kurabayashi, M.; Hasegawa, A.; Ohmori, S.; Nakamura, Tomonori; Yamamoto, K.

In: Journal of Clinical Pharmacy and Therapeutics, Vol. 37, No. 4, 08.2012, p. 481-485.

Research output: Contribution to journalArticle

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, vol. 37, no. 4, pp. 481-485. https://doi.org/10.1111/j.1365-2710.2011.01317.x
Nakamura, K. ; Obayashi, K. ; Araki, T. ; Aomori, Tohru ; Fujita, Y. ; Okada, Y. ; Kurabayashi, M. ; Hasegawa, A. ; Ohmori, S. ; Nakamura, Tomonori ; Yamamoto, K. / CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. In: Journal of Clinical Pharmacy and Therapeutics. 2012 ; Vol. 37, No. 4. pp. 481-485.
@article{9bc571326474417a96682e10699edf59,
title = "CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects",
abstract = "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.",
keywords = "CYP4F2, oxide, polymorphism, reductase, vitamin K, warfarin",
author = "K. Nakamura and K. Obayashi and T. Araki and Tohru Aomori and Y. Fujita and Y. Okada and M. Kurabayashi and A. Hasegawa and S. Ohmori and Tomonori Nakamura and K. Yamamoto",
year = "2012",
month = "8",
doi = "10.1111/j.1365-2710.2011.01317.x",
language = "English",
volume = "37",
pages = "481--485",
journal = "Journal of Clinical Pharmacy and Therapeutics",
issn = "0269-4727",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects

AU - Nakamura, K.

AU - Obayashi, K.

AU - Araki, T.

AU - Aomori, Tohru

AU - Fujita, Y.

AU - Okada, Y.

AU - Kurabayashi, M.

AU - Hasegawa, A.

AU - Ohmori, S.

AU - Nakamura, Tomonori

AU - Yamamoto, K.

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - CYP4F2

KW - oxide

KW - polymorphism

KW - reductase

KW - vitamin K

KW - warfarin

UR - http://www.scopus.com/inward/record.url?scp=84863445646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863445646&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2710.2011.01317.x

DO - 10.1111/j.1365-2710.2011.01317.x

M3 - Article

C2 - 22172097

AN - SCOPUS:84863445646

VL - 37

SP - 481

EP - 485

JO - Journal of Clinical Pharmacy and Therapeutics

JF - Journal of Clinical Pharmacy and Therapeutics

SN - 0269-4727

IS - 4

ER -