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Evaluation of common polymorphism of CYP2C9 in Warfarin-treated patients
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F. Rad   , M. Hamidpour , H. Saadat , B. Poopak |
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| Keywords: Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein٬ human, Vitamin K |
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Full-Text [PDF 280 kb]
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Type of Study: Research |
Subject:
Hematology
Published: 2016/01/5
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Full-Text: (2182 Views) |
References :
- Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999; 353(9154): 717-9.
- Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119(1 Suppl): 8S-21S.
- Wen M, Lee M, Chen J, Chuang H, Lu L, Chen CH, et al. Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes. Clin Pharmacol Ther 2008; 84(1): 83-9.
- Caldwell MD, Berg RL, Zhang KQ, Glurich I, Schmelzer JR, Yale SH, et al. Evaluation of genetic factors for warfarin dose prediction. Clin Med Res 2007; 5(1): 8-16.
- Stubbins MJ, Harries LW, Smith G, Tarbit MH, Wolf CR. Genetic analysis of the human cytochrome P450 CYP2C9 locus. Pharmacogenetics 1996; 6(5): 429-39.
- Xie HG, Kim RB, Wood AJ, Stein CM. Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol 2001; 41(1): 815-50.
- Lindh JD, Holm 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): 365-75.
- Cooper GM, Johnson JA, Langaee TY, Feng H, Stanaway IB, Schwarz UI, et al. A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose. Blood 2008; 112(4): 1022-7.
- Teichert M, Eijgelsheim M, Uitterlinden AG, Buhre PN, Hofman A, De Smet PA, et al. Dependency of phenprocoumon dosage on polymorphisms in the VKORC1, CYP2C9, and CYP4F2 genes. Pharmacogenet Genomics 2011; 21(1): 26-34.
- D’Andrea G, D’Ambrosio R, Margaglione M. Oral
anticoagulants: pharmacogenetics: relationship between genetic and non-genetic factors. Blood Rev 2008; 22(3): 127-40.
- Voora D, Eby C, Linder MW, Milligan PE, Bukaveckas BL, McLeod HL, et al. Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype. Thromb Haemost 2005; 93(4): 700-5.
- Miao L, Yang J, Huang C, Shen Z. Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients. Eur J Clin Pharmacol 2007; 63(12): 1135-41.
- Takahashi H, Wilkinson GR, Caraco Y, Muszkat M, Kim RB, Kashima T, et al. Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Clin Pharmacol Ther 2003; 73(3): 253-63.
- Kim HS, Lee SS, Oh M, Jang YJ, Kim EY, Han IY, et al. Effect of CYP2C9 and VKORC1 genotypes on early-phase and steady-state warfarin dosing in Korean patients with mechanical heart valve replacement. Pharmacogenet Genomics 2009; 19(2): 103-12.
- Ngow HA, Wan KW, Teh L, Lee W, Harun R, Ismail R, et al. CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia. Singapore Med J 2009; 50(5): 490-3.
- Borgiani P, Ciccacci C, Forte V, Romano S, Federici G, Novelli G. Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians. Pharmacogenomics 2007; 50(5): 490-3.
- Oner Ozgon G, Langaee T, Feng H, Buyru N, Ulutin T, Hatemi A, et al. VKORC1 and CYP2C9
polymorphisms are associated with warfarin dose requirements in Turkish patients. Eur J Clin Pharmacol 2008; 64(9): 889-94.
- Tham LS, Goh BC, Nafziger A, Guo JY, Wang LZ, Soong R, 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(4): 346-55.
- Zhao F, Loke C, Rankin SC, Guo JY, Lee HS, Wu TS, et al. Novel CYP2C9 genetic variants in asian subjects and their influence on maintenance warfarin dose. Clin Pharmacol Ther 2004; 76(3): 210-9.
- Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, et al. Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther 2007; 83(2): 312-21.
- Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther 2011; 90(4): 625-9.
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Sci J Iran Blood Transfus Organ 2016; 12(4): 340-346
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Evaluation of common polymorphism of CYP2C9
in Warfarin-treated patients
Rad F.1, Hamidpour M.2, Saadat H.3, Poopak B.4
1Yasuj University of Medical Sciences, Yasuj, Iran
2Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Cardio-Vascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4School of Allied Medicine, Medical Branch of Islamic Azad University, Tehran, Iran
Abstract
Background and Objectives
Warfarin and other anticoagulant medications like Coumadin are widely prescribed by physicians to prevent ischemic events. A variety of factors such as sex, age and weight can affect warfarin dosage requirements. A clinical effect of warfarin depends on highly polymorphic drug-metabolizing (CYP2C9) enzymes. The objective of this study was to investigate the impact of CYP2C9*2, CYP2C9*3 polymorphisms on the variability of warfarin dosage requirements in Iranian population that were under warfarin therapy for different reasons.
Materials and Methods
The study included 100 patients with the mean age of 61.3 years. The restriction fragment length polymorphism method was used to identify polymorphisms of CYP2C9 (*1, *2, *3) in Iranian patients with ischemic heart disease in Peyvand Laboratory.
Results
Two-thirds (68.42%) of the patients had the wild-type (WT) CYP2C9*1*1 genotype; 10.53%, 18.95%, and 2.1% of the patients had CYP2C9 *1*2, *1*3, and *2*3 genotype, respectively. WT CYP2C9*1*1 genotype was associated with a higher daily warfarin dosage (4.58 ± 1.57 mg/day; p= 0.02) as compared to other CYP2C9 genotypes.
Conclusions
The Iranian study sample is characterized by high frequency *1*1 genotypes that determine a higher warfarin-loading dose. Analysis of CYP2C9 gene variants allows the prediction of warfarin dosage. These results can be used to individualize treatment with warfarin in Iranian patients.
Key words: Warfarin, Genetic Polymorphism, CYP2C9 protein ٬ human, Vitamin K
Received: 3 Mar 2015
Accepted: 24 May 2015
Correspondence: Poopak B., PhD of Hematology. Assistant Professor of School of Allied Medicine, Medical Branch of Islamic Azad University.
P.O.Box: 19395-1495, Tehran, Iran. Tel: (+9821) 22257438; Fax: (+9821) 22257438
E-mail: bpoopak@yahoo.com
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