Published by: Kowsar

Polymorphism Detection of VKORC1 and CYP2C9 Genes for Warfarin Dose Adjustment by Real-Time PCR

Siamak Mirab Samiee 1 , 2 , Samira Mohammadi Yeganeh 3 , Mahdi Paryan 4 , Houri Rezvan 2 , Ehsan Mostafavi 5 and Parvin Pasalar 6 , *
Authors Information
1 Food and Drug Laboratory Research Center, Ministry of Health and Medical Education, Tehran, IR Iran
2 Day General Hospital Laboratory, Tehran, IR Iran
3 Department of Biotechnology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
4 Department of Research and Development, Production and Research Complex, Pasteur Institute, Tehran, IR Iran
5 Department of Epidemiology, Pasteur Institute of Iran, Tehran, IR Iran
6 Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran
Article information
  • Thrita: March 01, 2014, 3 (1); e14033
  • Published Online: February 20, 2014
  • Article Type: Research Article
  • Received: August 4, 2013
  • Revised: September 15, 2013
  • Accepted: October 11, 2013
  • DOI: 10.5812/thrita.14033

To Cite: Samiee S M, Mohammadi Yeganeh S, Paryan M, Rezvan H, Mostafavi E, et al. Polymorphism Detection of VKORC1 and CYP2C9 Genes for Warfarin Dose Adjustment by Real-Time PCR, Thrita. 2014 ;3(1):e14033. doi: 10.5812/thrita.14033.

Copyright © 2014, Thrita. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Patients and Methods
4. Results
5. Discussion
  • 1. Cavallari LH, Limdi NA. Warfarin pharmacogenomics. Curr Opin Mol Ther. 2009; 11(3): 243-51[PubMed]
  • 2. Gage BF. Pharmacogenetics-based coumarin therapy. Hematology Am Soc Hematol Educ Program. 2006; : 467-73[DOI][PubMed]
  • 3. Hall AM, Wilkins MR. Warfarin: a case history in pharmacogenetics. Heart. 2005; 91(5): 563-4[DOI][PubMed]
  • 4. Lefferts JA, Schwab MC, Dandamudi UB, Lee HK, Lewis LD, Tsongalis GJ. Warfarin genotyping using three different platforms. Am J Transl Res. 2010; 2(4): 441-6[PubMed]
  • 5. Moyer TP, O'Kane DJ, Baudhuin LM, Wiley CL, Fortini A, Fisher PK, et al. Warfarin sensitivity genotyping: a review of the literature and summary of patient experience. Mayo Clin Proc. 2009; 84(12): 1079-94[DOI][PubMed]
  • 6. Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives. Thromb Res. 2007; 120(1): 1[DOI][PubMed]
  • 7. Azarpira N, Namazi S, Hendijani F, Banan M, Darai M. Investigation of allele and genotype frequencies of CYP2C9, CYP2C19 and VKORC1 in Iran. Pharmacol Rep. 2010; 62(4): 740-6[PubMed]
  • 8. Baniasadi S, Beizaee S, Kazemi B, Behzadnia N, Shafaghi B, Bandehpour M, et al. Novel VKORC1 mutations associated with warfarin sensitivity. Cardiovasc Ther. 2011; 29(4)-5[DOI][PubMed]
  • 9. D'Andrea G, D'Ambrosio RL, Di Perna P, Chetta M, Santacroce R, Brancaccio V, et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood. 2005; 105(2): 645-9[DOI][PubMed]
  • 10. Greer FR. Vitamin K the basics--what's new? Early Hum Dev. 2010; 86 Suppl 1: 43-7[DOI][PubMed]
  • 11. Pasmant E, de Beauvoir C, Plessier A, Labreuche J, Bezeaud A. VKORC1 and CYP2C9 genetic polymorphisms in hepatic or portal vein thrombosis. Thromb Res. 2010; 126(2)-6[DOI][PubMed]
  • 12. Zhou SF, Zhou ZW, Huang M. Polymorphisms of human cytochrome P450 2C9 and the functional relevance. Toxicology. 2010; 278(2): 165-88[DOI][PubMed]
  • 13. Ghadam P, Sharifian R, Farsangi ZJ, Kianmehr Z, Lak M. CYP2C9 gene analysis of some Iranian hypersensitive patients to warfarin. Pak J Biol Sci. 2009; 12(16): 1160-3[PubMed]
  • 14. Namazi S, Azarpira N, Hendijani F, Khorshid MB, Vessal G, Mehdipour AR. The impact of genetic polymorphisms and patient characteristics on warfarin dose requirements: a cross-sectional study in Iran. Clin Ther. 2010; 32(6): 1050-60[DOI][PubMed]
  • 15. Zand N, Tajik N, Moghaddam AS, Milanian I. Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population. Clin Exp Pharmacol Physiol. 2007; 34(1-2): 102-5[DOI][PubMed]
  • 16. Sinxadi P, Blockman M. Warfarin resistance. Cardiovasc J Afr. 2008; 19(4): 215-7[PubMed]
  • 17. Loeliger EA, Poller L, Samama M, Thomson JM, Van den Besselaar AM, Vermylen J, et al. Questions and answers on prothrombin time standardisation in oral anticoagulant control. Thromb Haemost. 1985; 54(2): 515-7[PubMed]
  • 18. Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH. A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006; 62(5): 617-20[DOI][PubMed]
  • 19. Kimura R, Miyashita K, Kokubo Y, Akaiwa Y, Otsubo R, Nagatsuka K, 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(2): 181-6[DOI][PubMed]
  • 20. Yoshizawa M, Hayashi H, Tashiro Y, Sakawa S, Moriwaki H, Akimoto T, et al. Effect of VKORC1-1639 G>A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients. Thromb Res. 2009; 124(2): 161-6[DOI][PubMed]
  • 21. Steimer W, Zopf K, von Amelunxen S, Pfeiffer H, Bachofer J, Popp J, et al. Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clin Chem. 2004; 50(9): 1623-33[DOI][PubMed]
  • 22. Mushiroda T, Ohnishi Y, Saito S, Takahashi A, Kikuchi Y, Saito S, et al. Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients. J Hum Genet. 2006; 51(3): 249-53[DOI][PubMed]
  • 23. Hamdy SI, Hiratsuka M, Narahara K, El-Enany M, Moursi N, Ahmed MS, et al. Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population. Br J Clin Pharmacol. 2002; 53(6): 596-603[PubMed]
  • 24. Adithan C, Gerard N, Vasu S, Balakrishnan R, Shashindran CH, Krishnamoorthy R. Allele and genotype frequency of CYP2C9 in Tamilnadu population. Eur J Clin Pharmacol. 2003; 59(8-9): 707-9[DOI][PubMed]
  • 25. Arvanitidis K, Ragia G, Iordanidou M, Kyriaki S, Xanthi A, Tavridou A, et al. Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population. Fundam Clin Pharmacol. 2007; 21(4): 419-26[DOI][PubMed]
  • 26. Scordo MG, Caputi AP, D'Arrigo C, Fava G, Spina E. Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population. Pharmacol Res. 2004; 50(2): 195-200[DOI][PubMed]
  • 27. Yasar U, Eliasson E, Dahl ML, Johansson I, Ingelman-Sundberg M, Sjoqvist F. Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population. Biochem Biophys Res Commun. 1999; 254(3): 628-31[DOI][PubMed]
  • 28. Herman D, Locatelli I, Grabnar I, Peternel P, Stegnar M, Mrhar A, et al. Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose. Pharmacogenomics J. 2005; 5(3): 193-202[DOI][PubMed]
  • 29. Gaikovitch EA, Cascorbi I, Mrozikiewicz PM, Brockmoller J, Frotschl R, Kopke K, et al. Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol. 2003; 59(4): 303-12[DOI][PubMed]
  • 30. Huang SW, Li Q, Zhu SY, Li L, Xiong F, Jia YK, et al. SYBR Green-based real-time PCR assay for detection of VKORC1 and CYP2C9 polymorphisms that modulate warfarin dose requirement. Clin Chem Lab Med. 2009; 47(1): 26-31[DOI][PubMed]
  • 31. Aomori T, Yamamoto K, Oguchi-Katayama A, Kawai Y, Ishidao T, Mitani Y, et al. Rapid single-nucleotide polymorphism detection of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genes for the warfarin dose adjustment by the SMart-amplification process version 2. Clin Chem. 2009; 55(4): 804-12[DOI][PubMed]
  • 32. Kwon A, Jo SH, Im HJ, Jo YA, Park JY, Kang HJ, et al. Pharmacogenetic distribution of warfarin and its clinical significance in Korean patients during initial anticoagulation therapy. J Thromb Thrombolysis. 2011; 32(4): 467-73[DOI][PubMed]
  • 33. Howard R, Leathart JB, French DJ, Krishan E, Kohnke H, Wadelius M, et al. Genotyping for CYP2C9 and VKORC1 alleles by a novel point of care assay with HyBeacon(R) probes. Clin Chim Acta. 2011; 412(23-24): 2063-9[DOI][PubMed]
  • 34. Esmerian MO, Mitri Z, Habbal MZ, Geryess E, Zaatari G, Alam S, et al. Influence of CYP2C9 and VKORC1 polymorphisms on warfarin and acenocoumarol in a sample of Lebanese people. J Clin Pharmacol. 2011; 51(10): 1418-28[DOI][PubMed]
Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments