Role of Genetic Variations in the CYP2C9 Gene in Determining the Optimal Dose of Warfarin in a Group of Syrian Patients
DOI:
https://doi.org/10.37285/ijpsn.2019.12.2.8Abstract
Genetic variations in drug metabolizing hepatic CYP2C9 gene determine the optimal dose for many drugs including anticoagulants such as warfarin. Here we sought to detect the frequency distribution of genetic variations of CYP2C9 gene and to determine its potential role in the control of warfarin dose in Syrian patients. The study included 125 patients with high risk of thrombosis of adults who visited the Heart Disease & Surgery Hospital (HDSH) and Aleppo University Hospital (AUH) and treated with warfarin as oral anticoagulant therapy, and the dose-corrected by the international normalized ratio (INR) at least three months ago. Genomic DNA was extracted from blood samples, and genotype analysis for CYP2C9*2 and CYP2C9*3 variant alleles was done by polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Data were analyzed using SPSS version 20. The results obtained in this study suggest that Genotype frequency distribution of CYP2C9*2 and CYP2C9*3 variant alleles was found to be different from other populations and has significant effect on warfarin dose requirement (p<0.05). It is concluded that there is a need to include CYP2C9 genetic variations detection tests in the warfarin dosing algorithm, as this has an important role in reducing serious hemorrhagic complications, especially in patients with the CYP2C9*2/*2 and CYP2C9*3/*3 homozygous mutant genotypes.
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Keywords:
Genetic Variations, CYP2C9, Warfarin Dose, Syria
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Published
2019-03-31
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1.
Shayah K, Ghrewati A, Mohammad YA, Hadid I. Role of Genetic Variations in the CYP2C9 Gene in Determining the Optimal Dose of Warfarin in a Group of Syrian Patients. Scopus Indexed [Internet]. 2019 Mar. 31 [cited 2024 Sep. 19];12(2):4505-11. Available from: https://ijpsnonline.com/index.php/ijpsn/article/view/296
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References
Alzahrani AM, Ragia G, Hanieh H and Manolopoulos VG. (2013). Genotyping of CYP2C9 and VKORC1 in the Arabic Population of Al-Ahsa, Saudi Arabia. Bio Med Research International, Volume 2013, Article ID 315980, 6 pages.
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M and Palareti G. (2008). Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 8th ed. Chest 133(6): 160S-198S.
Ayesh BM, Abu Shaaban AS and Abed AA. (2018). Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin dose in Gaza-Palestine. Future Sci. OA 4(3), FSO276.
Bazan NS, Sabry NA, Rizk A., Mokhtar S and Badary OA. (2014). Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism. Ir J Med Sci 183(2): 161-172.
Bazan NS, Sabry NA, Rizk A, Mokhtar S and Badary O. (2012). Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients. Int J Clin Pharm 34(6): 837-844.
Buzoianu AD, Trifa AP, Mures¸ anu DF, Cris ¸an S. (2012). Analysis of CYP2C9*2, CYP2C9*3 and VKORC1-1639 G>A polymorphisms in a population from South-Eastern Europe. J Cell Mol Med 16(12): 2919-2924.
Cini M, Legnani C, Cosmi B, Guazzaloca G, Valdrè L, Frascaro M and Palareti G. (2012). A new warfarin dosing algorithm including VKORC1 3730 G >A polymorphism: comparison with results obtained by other published algorithms. Eur J Clin
Pharmacol 68(8): 1167-1174.
Dean L. (2012). Warfarin therapy and VKORC1 and CYP genotype. In Medical Genetics Summaries (Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B and Malheiro A), National Center for Biotechnology Information (US), Bethesda (MD). pp 485-503.
El Din MS, Amin DG, Ragab SB, Ashour EE, Mohamed MH and Mohamed AM. (2012). Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen. Int J Lab Hematol 34(5): 517-524.
Finkelman BS, French B, Bershaw L, Brensinger CM, Streiff MB, Epstein AE and Kimmel SE. (2016). Predicting prolonged dose titration in patients starting warfarin. Pharmacoepidemiol. Drug Saf. 25(11): 1228-1235.
Gaikwad T, Ghosh K, Kulkarni B, Kulkarni V, Ross C and Shetty S. (2013). Influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin dosage, over anticoagulation and other adverse outcomes in Indian population. Eur J Pharmacol. 710(1-3): 80-84.
Gan GG, Phipps ME, Lee MMT, Lu LS, Subramaniam RY, Bee PC and Chang SH. (2010). Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. Ann Hematol DOI 10.1007/s00277-010-1119-6.
Gong IY, Schwarz UI, Crown N, Dresser GK, Lazo-Langner A, Zou G, Roden DM, Stein CM, Rodger M, Wells PS, Kim RB and Tirona RG. (2011). Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation. PLoS One 6(11): e27808.
Jureidini ID, Chamseddine N, Keleshian S, Naoufal R, Zahed L and Hakime N. (2011). Pharmacogenetics of coumarin dosing: prevalence of CYP2C9 and VKORC1 polymorphisms in the Lebanese population. Genetic Testing and Molecular Biomarkers 15 (11): 827-830.
Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE and Altman RB. (2011). Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin. Pharmacol. Ther. 90(4): 625-629.
Kaminsky LS, Zhang ZY. (1997). Human P450 metabolism of warfarin. Pharmacol Ther 73(1): 67-74.
Khoury G and sheikh-Taha M. (2014). Effect of age and sex on warfarin dosing. Clinical Pharmacology: Advances and Applications 6: 103-106.
Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. (2009). Estimation of the warfarin dose with clinical and pharmacogenetic data. International Warfarin Pharmacogenetics Consortium. N Engl J Med 360(8):753-764.
Lacy CF, Armstrong LL, Goldman MP and Lanco LL. (2008). Drug Information Handbook, 17th ed. Lexi-Comp, Inc, Hudson Ohio.
Liu Y, Yang J, Xu Q, Gao L, Zhang Y, Zhang Y, Wang H, Lu C, Zhao Y and Yin T. (2012). Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients. Thromb Res 130(3): 435-440.
Mirghani RA, Chowdhary G and Elghazali G. (2011). Distribution of the major Cytochrome P450 (CYP) 2C9 genetic variants in a Saudi population. Basic Clin Pharmacol Toxicol 109(2): 111-114.
Madhan S, Kumari DK, Kumar DT, Balachander J and Adithan C. (2013). Effect of CYP2C9 and VKORC1 Genetic Polymorphisims on Warfarin Dose Requirement in South Indian Population. Ind J Physiol Pharmacol 57(3): 308-317.
Mazzaccara C, Conti V, Liguori R, Simeon V, Toriello M, Severini A, Perricone C, Meccariello A, Meccariello P, Vitale DF, Filippelli A and Sacchetti L. (2013). Warfarin anticoagulant therapy: a southern Italy pharmacogenetics based dosing model. PLoS One 8(8): e71505.
Moridani M, Fu L, Selby R, Yun F, Sukovic T, Wong B and Cole DE. (2006). Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large anticoagulant clinic cohort. Clin Biochem 39(6): 606-12.
Natarajan S, Ponde CK, Rajani RM, Jijina F, Gursahani R, Dhairyawan PP and Ashavaid TF. (2013). Effect of CYP2C9 and VKORC1 genetic variations on warfarin dose requirements in Indian patients. Pharmacol Reports 65: 1375-1382.
Nahar R, Deb R, Saxena R, Puri RD and Verma IC. (2013). Variability in CYP2C9 allele frequency: a pilot study of its predicted impact on warfarin response among healthy South and North Indians. Pharmacol Rep 65(1): 187-194.
Poopak B, Rabieipoor S, Safari N, Naraghi E, Sheikhsofla F and Khosravipoor G. (2015). Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy. IJHOSCR 9(4): 185-192.
Pavani A, Naushad SM, Rupasree Y, Kumar TR, Malempati AR, Pinjala RK, Mishra RC and Kutala VK. (2012). Optimization of warfarin dose by population-specific pharmacogenomic algorithm. Pharmacogenomics J 12(4): 306-311.
Pautas E, Moreau C, Gouin-Thibault I, Golmard JL, Mahé I, Legendre C, Taillandier-Hériche E, Durand-Gasselin B, Houllier AM, Verrier P, Beaune P, Loriot MA and Siguret V. (2010). Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin Pharmacol Ther 87(1): 57-64.
Qayyum A, Najmi MH, Mansoor Q, Farooqi ZU, Naveed AK, Hanif A, Kazmi SAR and Ismail M. (2017). Frequency of Common CYP2C9 Polymorphisms and their impact on Warfarin Dose Requirement in Pakistani Population. Clinical and Applied Thrombosis/Hemostasis 23(7): 800-806.
Rusdiana T, Araki T, Nakamura T, Subarnas A and Yamamoto K. (2013). Responsiveness to low dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population. Eur J Clin Pharmacol. 69(3): 395-405.
Sabbagh A and Abajy MY. (2016). Investigation the single nucleotide polymorphism A1166C in angiotensin II type 1 receptor gene and it is association with hypertension in patients in Syria. Int J Academic Sci Res 4: 66-75.
Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK and Kamali F. (2005).The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood (7): 2329-2333.
Shahin MH, Khalifa SI, Gong Y, Hammad LN, Sallam MT, EL Shafey M, Ali SS, Mohamed ME, Langaee T and Johnsonf JI. (2011). Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. Pharmacogenet Genomics 21(3): 130-135.
Shalia KK, Doshi SM, Parikh S, Pawar PP, Divekar SS, Varma SP, Mehta R, Doctor T, Shah VK and Saranath D. (2012). Prevalence of VKORC1 and CYP2C9 gene polymorphisms in Indian population and its effect on warfarin response. J Assoc Physicians India 60: 34-38.
Suarez-kurtz G and Botton MR. (2013). Pharmacogenomics of warfarin in populations of African descent. Br J Clin Pharmacol 75(2): 334-346.
Sahib HA, Mohammed BI and Abdul-Majid BA. (2015). Genetic Polymorphism of CYP2C19 in a sample of Iraqi population. IJPBS 5(4): 54-60.
Schalekamp T, Brasse ´ BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC and de Boer A. (2006). VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects over anticoagulation. Clin Pharmacol Ther. 80(1): 13-22.
Tanira MO, Al-Mukhaini MK, Al-Hinai AT, Al Balushi KA and Ahmed IS. (2007). Frequency of CYP2C9 genotypes among Omani patients receiving warfarin and its correlation with warfarin dose. Community Genetics 10(1): 32-37.
White PJ. (2010). Patient Factors That Influence Warfarin Dose Response. Journal of Pharmacy Practice 23 (3): 194-204.
Wang TL, Li HL, Tjong WY, Chen QS, Wu GS, Zhu HT, Hou ZS, Xu S, Ma SJ, Wu M and Tai S. (2008). Genetic factors contribute to patient-specific warfarin dose for Han Chinese. Clin Chim Acta 396(1-2): 76-79.
Wang LS, Shang JJ, Shi SY, Zhang YQ, Lin J, Guo ZH, Wang YC, Tang J, Liu J, Liu YZ, Li Z, Tan ZR, Zhou HH, Jiang HH and Xie HT. (2013). Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage. Eur J Clin Pharmacol. 69(5):1113-1120.
Whitley HP, Fermo JD, Chumney ECG and Brzezinski WA. (2007) Effect of patient-specific factors on weekly warfarin dose. Ther Clin Risk Manag 3(3): 499-504.
Xie HG, Prasad HC, Kim RB and Stein CM. (2002). CYP2C9 allelic variants: ethnic distribution and functional significance. Advanced Drug Delivery Reviews 54(10): 1257-1270.
Yousef AM, Bulatova NR, Newman W, Hakooz N, Ismail S, Qusa H, Zahran F, Anwar Ababneh N, Hasan F, Zaloom I, Khayat G, Al-Zmili R, Naffa R and Al-Diab O. (2012). Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population. Molecular Biology Reports 39(10): 9423-9433.
Zohir N, Afifi1 R, Ahmed A, Aly Z, Elsobekey M, Kareem H and Helmy R. (2013). Role of CYP2C9, VKORC1 and Calumenin Genotypes in Monitoring Warfarin Therapy: An Egyptian Study. Clinical Science 1(1): 76-82.
Zand N, Tajik N, Moghaddam AS and Milanian I. (2007). Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population. Clin Exp Pharmacol Physiol 34(1-2): 102-105.
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M and Palareti G. (2008). Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 8th ed. Chest 133(6): 160S-198S.
Ayesh BM, Abu Shaaban AS and Abed AA. (2018). Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin dose in Gaza-Palestine. Future Sci. OA 4(3), FSO276.
Bazan NS, Sabry NA, Rizk A., Mokhtar S and Badary OA. (2014). Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism. Ir J Med Sci 183(2): 161-172.
Bazan NS, Sabry NA, Rizk A, Mokhtar S and Badary O. (2012). Validation of pharmacogenetic algorithms and warfarin dosing table in Egyptian patients. Int J Clin Pharm 34(6): 837-844.
Buzoianu AD, Trifa AP, Mures¸ anu DF, Cris ¸an S. (2012). Analysis of CYP2C9*2, CYP2C9*3 and VKORC1-1639 G>A polymorphisms in a population from South-Eastern Europe. J Cell Mol Med 16(12): 2919-2924.
Cini M, Legnani C, Cosmi B, Guazzaloca G, Valdrè L, Frascaro M and Palareti G. (2012). A new warfarin dosing algorithm including VKORC1 3730 G >A polymorphism: comparison with results obtained by other published algorithms. Eur J Clin
Pharmacol 68(8): 1167-1174.
Dean L. (2012). Warfarin therapy and VKORC1 and CYP genotype. In Medical Genetics Summaries (Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B and Malheiro A), National Center for Biotechnology Information (US), Bethesda (MD). pp 485-503.
El Din MS, Amin DG, Ragab SB, Ashour EE, Mohamed MH and Mohamed AM. (2012). Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen. Int J Lab Hematol 34(5): 517-524.
Finkelman BS, French B, Bershaw L, Brensinger CM, Streiff MB, Epstein AE and Kimmel SE. (2016). Predicting prolonged dose titration in patients starting warfarin. Pharmacoepidemiol. Drug Saf. 25(11): 1228-1235.
Gaikwad T, Ghosh K, Kulkarni B, Kulkarni V, Ross C and Shetty S. (2013). Influence of CYP2C9 and VKORC1 gene polymorphisms on warfarin dosage, over anticoagulation and other adverse outcomes in Indian population. Eur J Pharmacol. 710(1-3): 80-84.
Gan GG, Phipps ME, Lee MMT, Lu LS, Subramaniam RY, Bee PC and Chang SH. (2010). Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations. Ann Hematol DOI 10.1007/s00277-010-1119-6.
Gong IY, Schwarz UI, Crown N, Dresser GK, Lazo-Langner A, Zou G, Roden DM, Stein CM, Rodger M, Wells PS, Kim RB and Tirona RG. (2011). Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation. PLoS One 6(11): e27808.
Jureidini ID, Chamseddine N, Keleshian S, Naoufal R, Zahed L and Hakime N. (2011). Pharmacogenetics of coumarin dosing: prevalence of CYP2C9 and VKORC1 polymorphisms in the Lebanese population. Genetic Testing and Molecular Biomarkers 15 (11): 827-830.
Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, Anderson JL, Kimmel SE, Lee MT, Pirmohamed M, Wadelius M, Klein TE and Altman RB. (2011). Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin. Pharmacol. Ther. 90(4): 625-629.
Kaminsky LS, Zhang ZY. (1997). Human P450 metabolism of warfarin. Pharmacol Ther 73(1): 67-74.
Khoury G and sheikh-Taha M. (2014). Effect of age and sex on warfarin dosing. Clinical Pharmacology: Advances and Applications 6: 103-106.
Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, Limdi NA, Page D, Roden DM, Wagner MJ, Caldwell MD, Johnson JA. (2009). Estimation of the warfarin dose with clinical and pharmacogenetic data. International Warfarin Pharmacogenetics Consortium. N Engl J Med 360(8):753-764.
Lacy CF, Armstrong LL, Goldman MP and Lanco LL. (2008). Drug Information Handbook, 17th ed. Lexi-Comp, Inc, Hudson Ohio.
Liu Y, Yang J, Xu Q, Gao L, Zhang Y, Zhang Y, Wang H, Lu C, Zhao Y and Yin T. (2012). Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients. Thromb Res 130(3): 435-440.
Mirghani RA, Chowdhary G and Elghazali G. (2011). Distribution of the major Cytochrome P450 (CYP) 2C9 genetic variants in a Saudi population. Basic Clin Pharmacol Toxicol 109(2): 111-114.
Madhan S, Kumari DK, Kumar DT, Balachander J and Adithan C. (2013). Effect of CYP2C9 and VKORC1 Genetic Polymorphisims on Warfarin Dose Requirement in South Indian Population. Ind J Physiol Pharmacol 57(3): 308-317.
Mazzaccara C, Conti V, Liguori R, Simeon V, Toriello M, Severini A, Perricone C, Meccariello A, Meccariello P, Vitale DF, Filippelli A and Sacchetti L. (2013). Warfarin anticoagulant therapy: a southern Italy pharmacogenetics based dosing model. PLoS One 8(8): e71505.
Moridani M, Fu L, Selby R, Yun F, Sukovic T, Wong B and Cole DE. (2006). Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large anticoagulant clinic cohort. Clin Biochem 39(6): 606-12.
Natarajan S, Ponde CK, Rajani RM, Jijina F, Gursahani R, Dhairyawan PP and Ashavaid TF. (2013). Effect of CYP2C9 and VKORC1 genetic variations on warfarin dose requirements in Indian patients. Pharmacol Reports 65: 1375-1382.
Nahar R, Deb R, Saxena R, Puri RD and Verma IC. (2013). Variability in CYP2C9 allele frequency: a pilot study of its predicted impact on warfarin response among healthy South and North Indians. Pharmacol Rep 65(1): 187-194.
Poopak B, Rabieipoor S, Safari N, Naraghi E, Sheikhsofla F and Khosravipoor G. (2015). Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy. IJHOSCR 9(4): 185-192.
Pavani A, Naushad SM, Rupasree Y, Kumar TR, Malempati AR, Pinjala RK, Mishra RC and Kutala VK. (2012). Optimization of warfarin dose by population-specific pharmacogenomic algorithm. Pharmacogenomics J 12(4): 306-311.
Pautas E, Moreau C, Gouin-Thibault I, Golmard JL, Mahé I, Legendre C, Taillandier-Hériche E, Durand-Gasselin B, Houllier AM, Verrier P, Beaune P, Loriot MA and Siguret V. (2010). Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients. Clin Pharmacol Ther 87(1): 57-64.
Qayyum A, Najmi MH, Mansoor Q, Farooqi ZU, Naveed AK, Hanif A, Kazmi SAR and Ismail M. (2017). Frequency of Common CYP2C9 Polymorphisms and their impact on Warfarin Dose Requirement in Pakistani Population. Clinical and Applied Thrombosis/Hemostasis 23(7): 800-806.
Rusdiana T, Araki T, Nakamura T, Subarnas A and Yamamoto K. (2013). Responsiveness to low dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population. Eur J Clin Pharmacol. 69(3): 395-405.
Sabbagh A and Abajy MY. (2016). Investigation the single nucleotide polymorphism A1166C in angiotensin II type 1 receptor gene and it is association with hypertension in patients in Syria. Int J Academic Sci Res 4: 66-75.
Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK and Kamali F. (2005).The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood (7): 2329-2333.
Shahin MH, Khalifa SI, Gong Y, Hammad LN, Sallam MT, EL Shafey M, Ali SS, Mohamed ME, Langaee T and Johnsonf JI. (2011). Genetic and nongenetic factors associated with warfarin dose requirements in Egyptian patients. Pharmacogenet Genomics 21(3): 130-135.
Shalia KK, Doshi SM, Parikh S, Pawar PP, Divekar SS, Varma SP, Mehta R, Doctor T, Shah VK and Saranath D. (2012). Prevalence of VKORC1 and CYP2C9 gene polymorphisms in Indian population and its effect on warfarin response. J Assoc Physicians India 60: 34-38.
Suarez-kurtz G and Botton MR. (2013). Pharmacogenomics of warfarin in populations of African descent. Br J Clin Pharmacol 75(2): 334-346.
Sahib HA, Mohammed BI and Abdul-Majid BA. (2015). Genetic Polymorphism of CYP2C19 in a sample of Iraqi population. IJPBS 5(4): 54-60.
Schalekamp T, Brasse ´ BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC and de Boer A. (2006). VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects over anticoagulation. Clin Pharmacol Ther. 80(1): 13-22.
Tanira MO, Al-Mukhaini MK, Al-Hinai AT, Al Balushi KA and Ahmed IS. (2007). Frequency of CYP2C9 genotypes among Omani patients receiving warfarin and its correlation with warfarin dose. Community Genetics 10(1): 32-37.
White PJ. (2010). Patient Factors That Influence Warfarin Dose Response. Journal of Pharmacy Practice 23 (3): 194-204.
Wang TL, Li HL, Tjong WY, Chen QS, Wu GS, Zhu HT, Hou ZS, Xu S, Ma SJ, Wu M and Tai S. (2008). Genetic factors contribute to patient-specific warfarin dose for Han Chinese. Clin Chim Acta 396(1-2): 76-79.
Wang LS, Shang JJ, Shi SY, Zhang YQ, Lin J, Guo ZH, Wang YC, Tang J, Liu J, Liu YZ, Li Z, Tan ZR, Zhou HH, Jiang HH and Xie HT. (2013). Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage. Eur J Clin Pharmacol. 69(5):1113-1120.
Whitley HP, Fermo JD, Chumney ECG and Brzezinski WA. (2007) Effect of patient-specific factors on weekly warfarin dose. Ther Clin Risk Manag 3(3): 499-504.
Xie HG, Prasad HC, Kim RB and Stein CM. (2002). CYP2C9 allelic variants: ethnic distribution and functional significance. Advanced Drug Delivery Reviews 54(10): 1257-1270.
Yousef AM, Bulatova NR, Newman W, Hakooz N, Ismail S, Qusa H, Zahran F, Anwar Ababneh N, Hasan F, Zaloom I, Khayat G, Al-Zmili R, Naffa R and Al-Diab O. (2012). Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population. Molecular Biology Reports 39(10): 9423-9433.
Zohir N, Afifi1 R, Ahmed A, Aly Z, Elsobekey M, Kareem H and Helmy R. (2013). Role of CYP2C9, VKORC1 and Calumenin Genotypes in Monitoring Warfarin Therapy: An Egyptian Study. Clinical Science 1(1): 76-82.
Zand N, Tajik N, Moghaddam AS and Milanian I. (2007). Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Iranian population. Clin Exp Pharmacol Physiol 34(1-2): 102-105.
