Biomeditsina va amaliyot jurnali, 2022 №3
Subject of the article
PREVALENCE OF ALLELES AND GENOTYPES OF TWO CYTOCHROME P450 HEPATIC SYSTEM ISOENZYMES (CYP2C19 and CYP2C9) AND THE MDR1 GENE AMONG HEALTHY VOLUNTEERS OF UZBEK NATIONALITY (123-129)
Authors
DAMINOVA Lola Turgunpulatovna, ABDASHIMOV Zafar Bakhtiyarovich
Institution
SamDTU
Abstract
The most clinically significant polymorphic markers of the CYP2C9 gene are the amino acid substitutions CYP2C9*2 (substitution in the 144 position of the polypeptide chain, leading to the substitution of the amino acid arginine for cysteine; 144Arg) and CYP2C9*3 (substitution in the 359 position of the polypeptide chain, leading to the substitution of the amino acid isoleucine for leucine; 359Leu). Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of widely used drugs. An important problem when taking NSAIDs are adverse drug reactions from the gastrointestinal tract at various levels - from dyspepsia to life-threatening complications such as bleeding or wound perforation. The formation of the risk of adverse drug reactions can be attributed to genetic factors, in particular, the polymorphism of the CYP2C9 gene. It has been shown that carriers of the "slow" alleles of the CYP2C9 gene (*2, *3) are more likely to develop gastric bleeding when taking NSAIDs (selecoxib, diclofenac, ibuprofen, naproxen or piroxicam)
Key words
alleles, genotypes, isoenzymes, volunteers, Uzbek nationality
Literature
1. Кляритская И.Л., Работягова Ю.С. Полиморфизм гена CYP2C19 и клиническое значение его определения. Крымский терапевтический журнал 2013;1:19-25. 2. Клинические рекомендации «Рациональное применение нестероидных противовоспалительных препаратов (НПВП) в клинической практике». Современная ревматология. 2015; 1: 4-23. 3. Обжерина А.Ю., Сычев Д.А., Муравьева Ю.В., Игнатьев И.В., Дмитриев В.А., Кукес В.Т Полиморфизм CYP2C9: новый фактор риска развития желудочно-кишечных осложнений при применении нестероидных противовоспалительных препаратов. Клиническая фармакология и фармакоэкономика. 2009; 2(5): 20-5. 4. Даминова Л.Т Мавлянов И.Р.Абдашимов З.Б. Места нестероидных противовоспалительных препаратов и анальгетиков в лечении скелетно-мышечной боли. Медицинский журнал Узбекистана, 2018, №2, С.80-84. 5. Blanco G., Martínez C., Ladero J.M. Interaction of CYP2C8 and CYP2C9 genotypes modifies the risk for nonsteroidal anti-inflammatory drugs-related acute gastrointestinal bleeding. // Pharmacogenet Genomics. – 2008. - vol.18(1). – P. 37–43. 6. Carbonell N., Verstuyft C., Massard J. CYP2C9*3 Loss-of-Function Allele Is Associated With Acute Upper Gastrointestinal Bleeding Related to the Use of NSAIDs Other Than Aspirin // Clin. Pharmacol. Ther. – 2010. - vol.87(6). – P. 693–698. 7. Denisenko NP, Sychev DA, Sizova ZM, et al. Urine metabolic ratio of omeprazole in relation to CYP2C19 polymorphisms in Russian peptic ulcer patients. Pharmgenomics Pers Med. 2017;10:253–259. DOI: 10.2147/PGPM.S141935 8. Estany-Gestal A., Salgado-Barreira A., Sánchez-Diz P., Figueiras A. Influence of CYP2C9 genetic variants on gastrointestinal bleeding associated with nonsteroidal anti-inflammatory drugs: a systematic critical review. // Pharmacogenet. Genomics. – 2011. -vol. 21(7). – P. 357– 364. 9. Furuta T, Sugimoto M, Shirai N. Individualized therapy for gastroesophageal reflux disease: potential impact of pharmacogenetic testing based on CYP2C19. Mol Diagn Ther. 2012;16(4):223–234. DOI: 10.2165/11634960-000000000-00000 10. Hunfeld N.G., Mathot R.A., Touw D.J. Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians // Br. J. Clin. Pharmacol. – 2008. – vol. 65(5). – P. 752–760. 11. Hunt R.H., Lanas A., Stichtenoth D.O., Scarpignato C. Myths and facts in the use of antiinflammatory drugs //Ann. Med. – 2009. - Vol. 41(6). – P. 423–437. 12. Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers Baldwin R.M., Ohlsson S., Pedersen R.S. et al. //Br. J. Clin. Pharmacol. – 2008. – vol. 65(5). – P. 767–774. 13. Ingelman-Sundberg M., Sim S.C., Gomez A., Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects // Pharmacol. Ther. – 2007. – vol.116(3). – P. 496–526. 14. Kaspera R., Totah R.A. Epoxyeicosatrienoic acids: formation, metabolism and potential role in tissue physiology and pathophysiology // Expert Opin. Drug Metab. Toxicol. – 2009. – vol.5(7). – P. 757–771. 15. Li-Wan-Po A., Girard T., Farndon P. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. // Br. J. Clin. Pharmacol. – 2010. – vol. 69(3): 222–230. 16. Ma J., Yang X.Y., Qiao L. CYP2C9 polymorphism in non-steroidal anti-inflammatory drugsinduced gastropathy // J. Dig. Dis. – 2008. – vol. 9(2): 79–83. 17. Martínez C, Blanco G, Ladero JM, et al. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol. 2004;141(2): 205–208. DOI: 10.1038/sj.bjp.0705623 18. Musumba C.O., Jorgensen A., Sutton L. et al. (2013) CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease // Clin. Pharmacol. Ther. 2013. - 93(2): 195–203. 19. Pedersen R.S., Brasch-Andersen C., Sim S.C. Linkage disequilibrium between the CYP2C19*17 allele and wildtype CYP2C8 and CYP2C9 alleles: identification of CYP2C haplotypes in healthy Nordic populations // Eur. J. Clin. Pharmacol. – 2010. – vol. 66(12): 1199–1205. 20. Pilotto A, Seripa D, Franceschi M, et al. Genetic susceptibility to nonsteroidal antiinflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology. 2007;133(2):465–471. 21. Preissner SC, Hoffmann MF, Preissner R Polymorphic cytochrome P450 enzymes (CYPs) and their role in personalized therapy // PLoS One 2013;8(12): e82562. 22. Scott S.A., Martis S., Peter I. et al. Identification of CYP2C19*4B: pharmacogenetic implications for drug metabolism including clopidogrel responsiveness // Pharmacogenomics J. – 2012. – vol. 12(4): 297–305. 23. Vogl S, Lutz RW, Schönfelder G, Lutz WK. CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug. PLoS One. 2015 Mar 16;10(3):e0120403. DOI: 10.1371/journal.pone.0120403