. Identification of CYP2C9, VKORC1 genotypes and recommendation of warfarin dose for Vietnamese cardiovascular patients

Nguyen Dang Ton, Nguyen Thi Thanh Hoa, Nguyen Phan Anh, Vu Phuong Nhung, Le Thi Bich Thao, Nguyen Hai Ha
Author affiliations

Authors

  • Nguyen Dang Ton
  • Nguyen Thi Thanh Hoa
  • Nguyen Phan Anh
  • Vu Phuong Nhung
  • Le Thi Bich Thao
  • Nguyen Hai Ha Institute of genome research

DOI:

https://doi.org/10.15625/1811-4989/17/4/14568

Keywords:

Warfarin, pharmacogenetics, CYP2C9 gene, VKORC1 gene, PCR-RFLP

Abstract

Warfarin is a well-known anticoagulant that capable of reducing the activity of vitamin K-dependent clotting factors. It has been widely used for cardiovascular patients. However, patient’s genotype of CYP2C9 and VKORC1 remarkably affects the metabolism of warfarin. This study aims to identify the CYP2C9 and VKORC1 genotypes of 96 Vietnamese patients suffering cardiodynia or myocardial infarction and establish their daily warfarin dose. The PCR-RFLP method was used to identified the CYP2C9*2, CYP2C9*3 and VKORC1 alleles. The result indicated that allelic frequencies for CYP2C9*3 were observed at 3% of investigated patients while CYP2C9*2 alleles and genotypes were not detected in this study population. Allele frequency of VKORC1 (c. -1639G>A) was observed at 84%. Base on the CYP2C9 and VKORC1 genotypes, we recommended the daily warfarin dose for of these patients.

Downloads

Download data is not yet available.

References

arrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE, Altman RB, Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther, 2011. 90(4): p. 625-9.

Takanashi K, T.H., Kobayashi K, Yasumori T, Hosakawa M, Chiba K, CYP2C9 Ile359 and Leu359 variants: enzyme kinetic study with seven substrates. Pharmacogenetics, 2000. 10(2): p. 95-104.

Sullivan-Klose TH, G.B., Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Goldstein JA. , The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. . Pharmacogenet genom, 1996. 6(4): p. 341-349.

Higashi MK, V.D., Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE, Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. Jama, 2002. 287(13): p. 1690-8.

Lindh JD, H.L., Andersson ML, Rane A, Influence of CYP2C9 genotype on warfarin dose requirements--a systematic review and meta-analysis. Eur J Clin Pharmacol, 2009. 65(4): p. 365-75.

D'Andrea G, D.A.R., Di Perna P, Chetta M, Santacroce R, Brancaccio V, Margaglione M, A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood, 2005. 105(2): p. 645-649.

Rieder MJ, R.A., Gage BF, Nickerson DA, Eby CS, McLeod HL, Rettie AE, Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med, 2005. 352(22): p. 2285-2293.

Scott SA, K.R., Peter I, Kornreich R, Desnick RJ, Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups. Pharmacogenom, 2010. 22(6): p. 781-791.

Takahashi H, W.G., Nutescu EA, Morita T, Ritchie MD, Scordo MG, Echizen H, Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans. Pharmacogenet genom, 2006. 16(2): p. 101-110.

FDA. Coumadin® tablets (warfarin sodium tablets, USP) crystalline; Coumadin® for injection (warfarin sodium for injection, USP). http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/009218s108lbl.pdf, 2010.

Vu NP, M.T., Tran NTB, Huynh HTT, Nguyen TD, Nguyen DT, Van Nong H, Lee MTM, Nguyen HH., Polymorphic analysis of CYP2C9 gene in Vietnamese population. Molecular biology reports, 2018. 45(5): p. 893-900.

Moreau C, P.E., Gouin-Thibault I, Golmard JL, Mahé I, Mulot C, Loriot MA, Siguret V, Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes. J Thromb Haemost, 2011. 9(4): p. 711-8.

Wen MS, L.M., Chen JJ, Chuang HP, Lu LS, Chen CH, Lee TH, Kuo CT, Sun FM, Chang YJ, Kuan PL, Chen YF, Charng MJ, Ray CY, Wu JY, Chen YT., Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes. Clin Pharmacol Ther, 2008. 84(1): p. 83-9.

Gage BF, E.C., Milligan PE, Banet GA, Duncan JR, McLeod HL, Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost, 2004. 91(1): p. 87-94.

Hillman MA, W.R., Caldwell MD, Berg RL, Glurich I, Burmester JK, Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype. Pharmacogenetics, 2004. 14: p. 539-47.

Sconce EA, K.T., Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK, Kamali F, The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood, 2005. 106(7): p. 2329-33.

Flockhart DA, O.K.D., Williams MS, Watson MS, Flockhart DA, Gage B, Gandolfi R, King R, Lyon E, Nussbaum R, O'Kane D, Schulman K, Veenstra D, Williams MS, Watson MS, Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genet Med, 2008. 10(2): p. 139–50.

Sangviroon A, P.D., Tassaneeyakul W, Namchaisiri J, Pharmacokinetic and pharmacodynamic variation associated with VKORC1 and CYP2C9 polymorphisms in Thai patients taking warfarin. Drug Metab Pharmacokinet, 2010. 25(6): p. 531-8.

Mushiroda T, O.Y., Saito S, Takahashi A, Kikuchi Y, Saito S, Shimomura H, Wanibuchi Y, Suzuki T, Kamatani N, Nakamura Y, Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients. J Hum Genet, 2006. 51(3): p. 249-53.

Chern HD, U.T., Fu YP, Cheng CW, CYP2C9 polymorphism and warfarin sensitivity in Taiwan Chinese. Clin Chim Acta, 2006. 367(1-2): p. 108-13.

Gan GG, P.M., Lee MM, Lu LS, Subramaniam RY, Bee PC, Chang SH, Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. Ann Hematol, 2011. 90(6): p. 635-41.

Rusdiana T, A.T., Nakamura T, Subarnas A, Yamamoto K. s, Responsiveness to low-dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population. Eur J Clin Pharmacol, 2013. 69(3): p. 395-405.

V, W., Pharmacogenomic effect of cytochrome P450 2C9 polymorphisms in different populations. Clin Appl Thromb Hemost, 2006. 12: p. 219-22.

Whirl-Carrillo, M., et al., Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther, 2012. 92(4): p. 414-7.

Published

02-11-2020

How to Cite

Dang Ton, N., Thanh Hoa, N. T., Phan Anh, N., Phuong Nhung, V., Bich Thao, L. T., & Hai Ha, N. (2020). . Identification of CYP2C9, VKORC1 genotypes and recommendation of warfarin dose for Vietnamese cardiovascular patients. Vietnam Journal of Biotechnology, 17(4), 589–594. https://doi.org/10.15625/1811-4989/17/4/14568

Issue

Section

Articles

Most read articles by the same author(s)

1 2 > >>