The prevalence of allelic variants of VKORC1, CYP2C9 and CYP4F2 genes in Zaporizhzhia region population
DOI:
https://doi.org/10.14739/2409-2932.2019.1.159128Keywords:
pharmacogenetics, warfarin, genotype, prevalenceAbstract
Objective – to determine the allele frequency of VKORC1, CYP2C9 and CYP4F2 genes in Zaporizhzhia region population.
Materials and methods. We investigated 94 individuals at the age of 56 (47; 62) years (men – 23, women – 71) who underwent preventive examination at the “Health” Diagnostic Center based on the ESMC “University Clinic” of the Zaporizhzhya State Medical University. To investigate the polymorphism of CYP2C9, CYP4F2, VKORC1 genes the polymorphic chain reaction method was used.
Results. It was established that in Zaporizhzhia region population, the frequency of detection of CYP2C9*2 polymorphic variants is: C/C – 80.9 %, C/T – 19.1 %, T/T – not observed; CYP2C9*3: A/A – 89.0 %, A/C – 11.0 %, C/C – not observed; CYP4F2: C/C – 50.0%, C/T – 40.4 %, T/T – 9.6 %; VKORC: 1 G/G – 40.4 %, G/A – 49.0 %, A/A – 10.6 %. It was discovered that the frequency of registration of polymorphic variants of genes CYP2C9, CYP4F2, VKORC1 varies in different geographic regions, that justifies the expediency of determining these genotypes for each population.
Conclusions. The implementation of pharmacogenetic testing based on the polymorphism of genes that affect warfarin metabolism for the warfarine dose titration is perspective.
References
Sychov, D. A. (2011) Rekomendacii po primeneniyu farmakogeneticheskogo testirovaniya v klinicheskoj praktike [Recommendations for the use of pharmacogenetic testing in clinical practice]. Kachestvennaya klinicheskaya praktika, 1, 4–10. [in Russian].
Gavrisyuk, E. V., Sychev, D. A., Kazakov, R. E., Kossovskaya, A. V., & Marinin, V. F. (2015) Opyt ispol’zovaniya farmakogeneticheskogo testirovaniya dlya personalizacii dozirovaniya varfarina v poliklinicheskikh usloviyakh [Experience in the use of pharmacogenetic testing for personalizing warfarin dosing in outpatient conditions]. Tikhookeanskij medicinskij zhurnal, 1, 60–62. [in Russian].
Sychov, O. S., Borodai, A. O., & Borodai, E. S. (2016) Prediktory vynyknennia serdtsevo-sudynnykh podii u patsientiv z fibryliatsiieiu ta tripotinniam perdserd neklapannoho pokhodzhennia [Predictors of cardiovascular outcomes in patients with non-valvular atrial fibrillation and flutter]. Ukrainskyi kardiolohichnyi zhurnal, 6, 64–75. [in Ukrainian].
Dziak, H. V., & Zharinov, O. Y. (2011). Fibrilliatsia peredserd [Atrial fibrillation]. Kyiv: Schetverta khvylia. [in Ukrainian].
Tseluyko, V. I., & Opolonskaya, N. A. (2013) Rasprostranennost’ faktorov riska tromboe'mbolicheskikh i gemorragicheskikh oslozhnenij sredi bol’nykh s fibrillyaciej predserdij [The Prevalence of Risk Factors for Thromboembolic and Hemorrhagic Complications among Patients with Atrial Fibrillation] Medicyna neotlozhnykh sostoyanij, 7(54), 65–69. [in Russian].
Daly, A. (2013). Optimal dosing of warfarin and other coumarin anticoagulants: the role of genetic polymorphisms. Archives of Toxicology, 87(3), 407–420. doi: 10.1007/s00204-013-1013-9
Johnson, J. A., Gong, L., Whirl-Carrillo, M., Gage, B. F., Scott, S. A., Stein, C. M., et al. (2011). Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing. Clinical Pharmacology & Therapeutics, 90(4), 625–629. doi: 10.1038/clpt.2011.185
Teh, L., Langmia, I., Fazleen Haslinda, M. H., Ngow, H. A., Roziah, M. J., Harun, R., et al. (2012). Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin. Journal of Clinical Pharmacy and Therapeutics, 37(2), 232–236. doi: 10.1111/j.1365-2710.2011.01262.x.
Zhu, Y., Shennan, M., Reynolds, K. K., Johnson, N. A., Herrnberger, M. R., Valdes, R. Jr., & Linder, M. W. (2007). Estimation of Warfarin Maintenance Dose Based on VKORC1 (-1639 G>A) and CYP2C9 Genotypes. Clinical Chemistry, 53(7), 1199–1205. doi: 10.1373/clinchem.2006.078139
Maliarchuk, I. V., Gorovenko, N. G., Krykunov, А. О., & Babochkina, A. R. (2014) Klinichne znachennia polimorfnoho varianta G1639A hena VKORC1 v indyvidualizatsii terapii varfarynom [The clinical significance of G1639A polymorphic variants of VKORC1 gene for individualized therapy with warfarin]. Ukrainskyi kardiolohichnyi zhurnal, 2, 100–105. [in Ukrainian].
Levkovich, N. M., & Gorovenko, N. G. (2013) Chastota rozpovsiudzhennia alelnykh variantiv *2 i *3 hena CYP2C9 u naselennia Ukrainy [Allele frequency distribution of CYP2C9 gene in Ukrainian population] Odeskyi medychnyi zhurnal, 2, 23–28. [in Ukrainian].
Rusdiana, T., Araki, T., Nakamura, T., Subarnas, A., & Yamamoto, K. (2012). Responsiveness to low-dose warfarin associated with genetic variants of VKORC1, CYP2C9, CYP2C19, and CYP4F2 in an Indonesian population. European Journal of Clinical Pharmacology, 69(3), 395–405. doi: 10.1007/s00228-012-1356-9
McDonald, M., Rieder, M., Nakano, M., Hsia, C., & Rettie, A. (2009). CYP4F2 Is a Vitamin K1 Oxidase: An Explanation for Altered Warfarin Dose in Carriers of the V433M Variant. Molecular Pharmacology, 75(6), 1337–1346. doi: 10.1124/mol.109.054833
Buzoianu, A., Trifa, A., Mureşanu, D., & Crişan, S. (2012). Analysis ofCYP2C9*2,CYP2C9*3andVKORC1-1639 G>A polymorphisms in a population from South-Eastern Europe. Journal of Cellular and Molecular Medicine, 16(12), 2919–2924. doi: 10.1111/j.1582-4934.2012.01606.x
Ross, K., Bigham, A., Edwards, M., Gozdzik, A., Suarez-Kurtz, G., & Parra, E. (2010). Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. Journal of Human Genetics, 55(9), 582–589. doi: 10.1038/jhg.2010.73.
Takahashi, H., Wilkinson, G. R., Nutescu, E. A., Morita, T., Ritchie, M. D., Scordo, M. G., et al. (2006). 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. Pharmacogenetics and Genomics, 16(2), 101–110. doi: 10.1097/01.fpc.0000184955.08453.a8
Cavallari, L. H., Momary, K. M., Patel, S. R., Shapiro, N. L., Nutescu, E., & Viana, M. A. (2011). Pharmacogenomics of Warfarin dose requirements in Hispanics. Blood Cells, Molecules, and Diseases, 46(2), 147–150. doi: 10.1016/j.bcmd.2010.11.005
Kimura, R., Miyashita, K., Kokubo, Y., Akaiwa, Y., Otsubo, R., Nagatsuka, K., et al. (2007). Genotypes of vitamin K epoxide reductase, γ-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. Thrombosis Research, 120(2), 181–186. doi: 10.1016/j.thromres.2006.09.007
Kamal El-Din, M. A., Farhan, M. S., El Shiha, R. I., El-Kaffas, R. M., & Mousa, S. M. (2014). Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients. Pediatric Drugs, 16(4), 337–341. doi: 10.1007/s40272-014-0073-5
Gan, G., Lee, M., Subramaniam, R., et al. (2012). Allele and Genotype frequencies of VKORC1 -1639G>A polymorphism in three different ethnic groups in Malaysia. Asia-Pacific Journal of Molecular Biology and Biotechnology, 20, 19–23.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
