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Thromb Haemost 2011; 105(06): 1100-1102
DOI: 10.1160/TH11-01-0018
Letters to the Editor
Schattauer GmbH

Effects of CYP4F2 and GGCX genetic variants on maintenance warfarin dose in a multiethnic Asian population

Sze Ling Chan
1   Department of Epidemiology and Public Health, National University of Singapore, Singapore
,
Boon Cher Goh
2   Department of Haematology-Oncology, National University Health System, Singapore
3   Cancer Science Institute of Singapore, Singapore
,
Kee Seng Chia
1   Department of Epidemiology and Public Health, National University of Singapore, Singapore
,
Benjamin Chuah
2   Department of Haematology-Oncology, National University Health System, Singapore
,
Andrea Wong
2   Department of Haematology-Oncology, National University Health System, Singapore
,
Robert Lim
2   Department of Haematology-Oncology, National University Health System, Singapore
,
Soo Chin Lee
2   Department of Haematology-Oncology, National University Health System, Singapore
3   Cancer Science Institute of Singapore, Singapore
› Author Affiliations Financial support:This study was supported by grants from the Singapore Cancer Syndicate (SCS-PN22R) and the National Medical Research Council, Singapore (NMRC/CSA/015/2009).
Further Information

Publication History

Received: 16 January 2011

Accepted after minor revision: 04 February 2011

Publication Date:
28 November 2017 (online)

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  • References

  • 1 Hirsh J, Fuster V, Ansell J. et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003; 107: 1692-1711.
    CrossrefPubMedSearch in Google Scholar
  • 2 Zhao F, Loke C, Rankin SC. et al. Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose. Clin Pharmacol Ther 2004; 76: 210-219.
    CrossrefPubMedSearch in Google Scholar
  • 3 Lee SC, Ng SS, Oldenburg J. et al. Interethnic variability of warfarin maintenance requirement is explained by VKORC1 genotype in an Asian population. Clin Pharmacol Ther 2006; 79: 197-205.
    CrossrefPubMedSearch in Google Scholar
  • 4 Caldwell M, Awad T, Johnson J. et al. CYP4F2 genetic variant alters required warfarin dose. Blood 2008; 111: 4106-4112.
    CrossrefPubMedSearch in Google Scholar
  • 5 Borgiani P, Ciccacci C, Forte V. et al. CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. Pharmacogenomics 2009; 10: 261-266.
    CrossrefPubMedSearch in Google Scholar
  • 6 Takeuchi F, McGinnis R, Bourgeois S. et al. A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 2009; 5: e1000433.
    CrossrefPubMedSearch in Google Scholar
  • 7 Pautas E, Moreau C, Gouin-Thibault I. et al. Genetic Factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) Are Predictor Variables for Warfarin Response in Very Elderly, Frail Inpatients. Clin Pharmacol Ther 2010; 87: 57-64.
    CrossrefPubMedSearch in Google Scholar
  • 8 Cen HJ, Zeng WT, Leng XY. et al. CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement. Br J Clin Pharmacol 2010; 70: 234-240.
    CrossrefPubMedSearch in Google Scholar
  • 9 Singh O, Sandanaraj E, Subramanian K. et al. The influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients. Drug Metab Pharmacokinet. 2010 epub ahead of print.
    PubMedSearch in Google Scholar
  • 10 Perini J, Struchiner C, Silva-Assunção E. et al. Impact of CYP4F2 rs2108622 on the stable warfarin dose in an admixed patient cohort. Clin Pharmacol Ther 2010; 87: 417-420.
    CrossrefPubMedSearch in Google Scholar
  • 11 Zhang JE, Jorgensen AL, Alfirevic A. et al. Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in patients initiated on warfarin therapy. Pharmacogenet Genomics 2009; 19: 781-789.
    CrossrefPubMedSearch in Google Scholar
  • 12 Lee M, Chen C, Chou C. et al. Genetic determinants of warfarin dosing in the Han-Chinese population. Pharmacogenomics 2009; 10: 1905-1913.
    CrossrefPubMedSearch in Google Scholar
  • 13 Cavallari LH, Langaee TY, Momary KM. et al. Genetic and clinical predictors of warfarin dose requirements in African Americans. Clin Pharmacol Ther 2010; 87: 459-464.
    CrossrefPubMedSearch in Google Scholar
  • 14 Carlquist JF, Horne BD, Mower C. et al. An evaluation of nine genetic variants related to metabolism and mechanism of action of warfarin as applied to stable dose prediction. J Thromb Thrombolysis 2010; 30: 358-364.
    CrossrefPubMedSearch in Google Scholar
  • 15 Kimura R, Miyashita K, Kokubo Y. et al. Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. Thromb Res 2007; 120: 181-186.
    CrossrefPubMedSearch in Google Scholar
  • 16 Wadelius M, Chen LY, Downes K. et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J 2005; 5: 262-270.
    CrossrefPubMedSearch in Google Scholar
  • 17 Cha P, Mushiroda T, Takahashi A. et al. High-resolution SNP and haplotype maps of the human gamma-glutamyl carboxylase gene (GGCX) and association study between polymorphisms in GGCX and the warfarin maintenance dose requirement of the Japanese population. J Hum Genet 2007; 52: 856-864.
    CrossrefPubMedSearch in Google Scholar
  • 18 Loebstein R, Vecsler M, Kurnik D. et al. Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9. Clin Pharmacol Ther 2005; 77: 365-372.
    CrossrefPubMedSearch in Google Scholar
  • 19 Wang TL, Li HL, Tjong WY. et al. Genetic factors contribute to patient-specific warfarin dose for Han Chinese. Clin Chim Acta 2008; 396: 76-79.
    CrossrefPubMedSearch in Google Scholar
  • 20 King C, Deych E, Milligan P. et al. Gamma-glutamyl carboxylase and its influence on warfarin dose. Thromb Haemost 2010; 104: 750-754.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Shikata E, Ieiri I, Ishiguro S. et al. Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity. Blood 2004; 103: 2630-2635.
    CrossrefPubMedSearch in Google Scholar
  • 22 Chen LY, Eriksson N, Gwilliam R. et al. Gamma-glutamyl carboxylase (GGCX) microsatellite and warfarin dosing. Blood 2005; 106: 3673-3674.
    CrossrefPubMedSearch in Google Scholar
  • 23 Caldwell MD, Berg RL, Zhang KQ. et al. Evaluation of genetic factors for warfarin dose prediction. Clin Med Res 2007; 5: 8-16.
    CrossrefPubMedSearch in Google Scholar
  • 24 Chan S, Thalamuthu A, Goh B. et al. Exon sequencing and association analysis of EPHX1 genetic variants with maintenance warfarin dose in a multiethnic Asian population. Pharmacogenet Genomics 2011; 21: 35-41.
    CrossrefPubMedSearch in Google Scholar
  • 25 Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 887-893.
    CrossrefPubMedSearch in Google Scholar
  • 26 Rieder MJ, Reiner AP, Rettie AE. Gamma-glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose. J Thromb Haemost 2007; 5: 2227-2234.
    CrossrefPubMedSearch in Google Scholar
  • 27 Tham LS, Goh BC, Nafziger A. et al. A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9. Clin Pharmacol Ther 2006; 80: 346-355.
    CrossrefPubMedSearch in Google Scholar
  • 28 R Development Core Team.. R: A Language and Environment for Statistical Computing. 2010 Available at: http://www.R-project.org.
    PubMed
  • 29 Pérez-Andreu V, Roldán V, Antón A. et al. Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy. Blood 2009; 113: 4977-4979.
    CrossrefPubMedSearch in Google Scholar
  • 30 Teichert M, Eijgelsheim M, Rivadeneira F. et al. A genome-wide association study of acenocoumarol maintenance dosage. Hum Mol Genet 2009; 18: 3758-3768.
    CrossrefPubMedSearch in Google Scholar
  • 31 Teichert M, Eijgelsheim M, Uitterlinden A. et al. Dependency of phenprocoumon dosage on polymorphisms in the VKORC1, CYP2C9, and CYP4F2 genes. Pharmacogenet Genomics 2011; 21: 26-34.
    CrossrefPubMedSearch in Google Scholar
  • 32 Cadamuro J, Dieplinger B, Felder T. et al. Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements. Eur J Clin Pharmacol 2010; 66: 253-260.
    CrossrefPubMedSearch in Google Scholar
  • 33 Luxembourg B, Schneider K, Sittinger K. et al. Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, F7, GGCX, CALU, EPHX1) gene variants on the initiation and maintenance phases of phenprocoumon therapy. Thromb Haemost 2011; 105: 169-180.
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Gauderman W, Morrison J. QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. 2006 Available at: http://hydra.usc.edu/gxe.
    PubMedSearch in Google Scholar