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Распространенность полиморфизмов генов CYP2C8, PTGS-1, 2, ассоциированных с чувствительностью к нестероидным противовоспалительным препаратам, среди этнических групп Северного Кавказа
Абдуллаев Ш.П., Денисенко Н.П., Мирзаев К.Б., Шуев Г.Н., Созаева Ж.А., Качанова А.А., Маммаев С.Н., Касаева Э.А., Гафуров Д.М., Гришина Е.А., Сычев Д.А. Распространенность полиморфизмов генов CYP2C8, PTGS-1, 2, ассоциированных с чувствительностью к нестероидным противовоспалительным препаратам, среди этнических групп Северного Кавказа. Терапевтический архив. 2021;93(11):1334–1339. DOI: 10.26442/00403660.2021.11.201220
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Abdullaev SP, Denisenko NP, Mirzaev KB, Shuev GN, Sozaeva ZhA, Kachanova AA, Mammaev SN, Kasaeva EA, Gafurov DM, Grishina EA, Sychev DA. CYP2C8, PTGS-1, 2 gene polymorphisms prevalence associated with sensitivity to non-steroidal anti-inflammatory drugs among North Caucasus ethnic groups. Terapevticheskii Arkhiv (Ter. Arkh.). 2021;93(11):1334–1339. DOI: 10.26442/00403660.2021.11.201220
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Аннотация
Цель. Изучить распространенность CYP2C8*3 (rs10509681; rs11572080), PTGS-1 (rs10306135; rs12353214) и PTGS-2 (rs20417) среди аварцев, даргинцев, лакцев и кумыков.
Материалы и методы. В исследовании приняли участие 400 добровольцев из 4 этнических групп Республики Дагестан: по 100 из аварской, даргинской, лакской и кумыкской этнических групп. Носительство полиморфных маркеров CYP2C8 и PTGS-1, 2 определялось методом полимеразной цепной реакции в реальном времени.
Результаты. Распространенность минорного аллеля CYP2C8 (rs10509681 составила: у аварцев – 5,5%, даргинцев – 10%, лакцев и кумыков – по 6,5%; CYP2C8 (rs11572080): у аварцев – 5,5%, даргинцев – 9,5%, лакцев – 6,5%, кумыков – 8,5%; PTGS-1 (rs10306135): у аварцев – 10,5%, даргинцев – 13,0%, лакцев – 9,5% и кумыков – 7,5%; PTGS-1 (rs12353214): у аварцев – 9,0%, даргинцев – 4,5%, лакцев – 7,5%, кумыков – 8,0%; PTGS-2 (rs20417): у аварцев – 1,0%, даргинцев – 2,5%, лакцев – 3,5%, кумыков – 5,0%. Достоверных различий между группами не выявлено.
Заключение. Изучение полиморфизмов генов CYP2C8 и PTGS-1 и 2 является перспективным для прогнозирования эффективности и безопасности терапии нестероидными противовоспалительными препаратами в связи с высокой распространенностью данных полиморфизмов в этнических группах Северного Кавказа.
Ключевые слова: фармакогенетика, этнические группы, CYP2C8, PTGS-1, PTGS-2, нестероидные противовоспалительные препараты
Материалы и методы. В исследовании приняли участие 400 добровольцев из 4 этнических групп Республики Дагестан: по 100 из аварской, даргинской, лакской и кумыкской этнических групп. Носительство полиморфных маркеров CYP2C8 и PTGS-1, 2 определялось методом полимеразной цепной реакции в реальном времени.
Результаты. Распространенность минорного аллеля CYP2C8 (rs10509681 составила: у аварцев – 5,5%, даргинцев – 10%, лакцев и кумыков – по 6,5%; CYP2C8 (rs11572080): у аварцев – 5,5%, даргинцев – 9,5%, лакцев – 6,5%, кумыков – 8,5%; PTGS-1 (rs10306135): у аварцев – 10,5%, даргинцев – 13,0%, лакцев – 9,5% и кумыков – 7,5%; PTGS-1 (rs12353214): у аварцев – 9,0%, даргинцев – 4,5%, лакцев – 7,5%, кумыков – 8,0%; PTGS-2 (rs20417): у аварцев – 1,0%, даргинцев – 2,5%, лакцев – 3,5%, кумыков – 5,0%. Достоверных различий между группами не выявлено.
Заключение. Изучение полиморфизмов генов CYP2C8 и PTGS-1 и 2 является перспективным для прогнозирования эффективности и безопасности терапии нестероидными противовоспалительными препаратами в связи с высокой распространенностью данных полиморфизмов в этнических группах Северного Кавказа.
Ключевые слова: фармакогенетика, этнические группы, CYP2C8, PTGS-1, PTGS-2, нестероидные противовоспалительные препараты
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Aim. Find the prevalence of CYP2C8*3 (rs10509681; rs11572080), PTGS-1 (rs10306135; rs12353214) and PTGS-2 (rs20417) alleles and genotypes in four ethnic groups among Laks, Avars, Dargins and Kumyks.
Materials and methods. The study involved 400 volunteers from four ethnic groups living in Republic of Dagestan: 100 participants from each group. Carriage of polymorphic markers was determined by reverse transcription polymerase chain reaction.
Results. Minor allele frequency of the CYP2C8 (rs10509681) was 5.5% in Avars, 10% in Dargins, Laks and Kumyks – 6.5% both; CYP2C8 (rs11572080) was 5.5% in Avars, 9.5% in Dargins, 6.5% in Laks, 8.5% in Kumyks; PTGS-1 (rs10306135) in Avars – 10.5%, in Dargins – 13.0%, in Laks – 9.5% and Kumyks – 7.5%; PTGS-1 (rs12353214) in Avars – 9.0%, in Dargins – 4.5%, in Laks – 7.5%, in Kumyks – 8.0%; PTGS-2 (rs20417) in Avars – 1.0%, in Dargins – 2.5%, in Laks – 3.5%, in Kumyks – 5.0%. There were no significant differences between groups.
Conclusion. The study of CYP2C8 and PTGS-1 and 2 gene polymorphisms is promising for predicting the effectiveness and safety of non-steroidal anti-inflammatory drug therapy, due to the high prevalence of these polymorphisms in ethnic groups in the North Caucasus.
Keywords: pharmacogenetics, ethnics, CYP2C8, PTGS-1, PTGS-2, non-steroidal anti-inflammatory drugs
Полный текст
Список литературы
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8. Tracy TS, Marra C, Wrighton SA, et al. Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol. 1997;52(4):293-8. DOI:10.1007/s002280050293
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DOI:10.2165/00003088-199732040-00002
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11. Karaźniewicz-Łada M, Luczak M, Główka F. Pharmacokinetic studies of enantiomers of ibuprofen and its chiral metabolites in humans with different variants of genes coding CYP2C8 and CYP2C9 isoenzymes. Xenobiotica. 2009;39(6):476-85. DOI:10.1080/00498250902862705
12. López-Rodríguez R, Novalbos J, Gallego-Sandín S, et al. Influence of CYP2C8 and CYP2C9 polymorphisms on pharmacokinetic and pharmacodynamic parameters of racemic and enantiomeric forms of ibuprofen in healthy volunteers. Pharmacol Res. 2008;58(1):77-84. DOI:10.1016/j.phrs.2008.07.004
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21. Lee YS, Kim H, Wu TX, et al. Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs. Clin Pharmacol Ther. 2006;79(5):407-18. DOI:10.1016/j.clpt.2006.01.013
22. Caciagli L, Bulayeva K, Bulayev O, et al. The key role of patrilineal inheritance in shaping the genetic variation of Dagestan highlanders. J Hum Genet. 2009;54(12):689-94. DOI:10.1038/jhg.2009.94
23. Yunusbayev B, Metspalu M, Järve M, et al. The Caucasus as an asymmetric semipermeable barrier to ancient human migrations. Mol Biol Evol. 2012;29(1):359-65. DOI:10.1093/molbev/msr221
24. Mirzaev KB, Fedorinov DS, Ivashchenko DV, Sychev DA. ADME pharmacogenetics: future outlook for Russia. Pharmacogenomics. 2019;20(11):847-65. DOI:10.2217/pgs-2019-0013
25. Ромодановский Д.П., Хапаев Б.А., Игнатьев И.В., и др. Частоты «медленных» аллельных вариантов генов, кодирующих изоферменты цитохрома Р450 CYP2D6, CYP2C19, CYP2C9 у карачаевцев и черкесов. Биомедицина. 2010;1(2):33-7 [Romodanovskij DP, Hapaev BA, Ignatev IV, et al. Frequencies of “slow” allelic variants of genes encoding cytochrome P450 isoenzymes CYP2D6, CYP2C19, CYP2C9 in Karachais and Circassians. Biomedicine. 2010;1(2):33-7 (in Russian)].
26. Батурин В.А., Царукян А.А., Колодийчук Е.В. Исследование полиморфизма гена CYP2C9 в этнических группах населения Ставропольского края. Медицинский вестник Северного Кавказа. 2014;9(1):45-8 [Baturin VA, Carukyan AA, Kolodijchuk EV. Study of CYP2C9 gene polymorphism in ethnic groups of Stavropol Krai. Medical Bulletin of the North Caucasus. 2014;9(1):45-8 (in Russian)]. DOI:10.14300/mnnc.2014.09013
27. Sychev DA, Abdullaev SP, Mirzaev KB, et al. Genetic determinants of dabigatran safety (CES1 gene rs2244613 polymorphism) in the Russian population: multi-ethnic analysis. Mol Biol Rep. 2019;46(3):2761-69. DOI:10.1007/s11033-019-04722-w
28. Mirzaev KB, Sychev DA, Ryzhikova KA, et al. Genetic Polymorphisms of Cytochrome P450 Enzymes and Transport Proteins in a Russian Population and Three Ethnic Groups of Dagestan. Genet Test Mol Biomarkers. 2017;21(12):747-53. DOI:10.1089/gtmb.2017.0036
29. Tang H, Quertermous T, Rodriguez B, et al. Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies. Am J Hum Genet. 2005;76(2):268-75. DOI:10.1086/427888
30. The ALlele FREquency Database. Available at: https://alfred.med.yale.edu/alfred/index.asp. Accessed: 10.05.2021.
31. GnomAD Exome. Available at: https://gnomad.broadinstitute.org/ Accessed: 10.05.2021.
32. Karafet TM, Bulayeva KB, Bulayev OA, et al. Extensive genome-wide autozygosity in the population isolates of Daghestan. Eur J Hum Genet. 2015;23(10):1405-12. DOI:10.1038/ejhg.2014.299
2. Ghlichloo I, Gerriets V. Nonsteroidal Anti-inflammatory Drugs (NSAIDs). 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK547742/ Accessed: 04.05.2021.
3. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging Dis. 2018;9(1):143-50. DOI:10.14336/AD.2017.0306
4. Каратеев А.Е., Насонов Е.Л., Ивашкин В.Т., и др. Рациональное использование нестероидных противовоспалительных препаратов. Клинические рекомендации. Научно-практическая ревматология. 2018;56:1-29 [Karateev AE, Nasonov EL, Ivashkin VT, et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical guidelines. Rheumatology Science and Practice. 2018;56:1-29 (in Russian)]. DOI:10.14412/1995-4484-2018-1-29
5. Agúndez JA, García-Martín E, Martínez C. Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert Opin Drug Metab Toxicol. 2009;5(6):607-20. DOI:10.1517/17425250902970998
6. Zhou SF, Zhou ZW, Huang M. Polymorphisms of human cytochrome P450 2C9 and the functional relevance. Toxicology. 2010;278(2):165‑88. DOI:10.1016/j.tox.2009.08.013
7. Theken KN, Lee CR, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2C9 and Nonsteroidal Anti-Inflammatory Drugs. Clin Pharmacol Ther. 2020;108(2):191-200. DOI:10.1002/cpt.1830
8. Tracy TS, Marra C, Wrighton SA, et al. Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol. 1997;52(4):293-8. DOI:10.1007/s002280050293
9. Davies NM, Anderson KE. Clinical pharmacokinetics of naproxen. Clin Pharmacokinet. 1997;32(4):268-93.
DOI:10.2165/00003088-199732040-00002
10. Zajic SC, Jarvis JP, Zhang P, et al. Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative. Pharmacogenet Genomics. 2019;29(3):49-57. DOI:10.1097/FPC.0000000000000364
11. Karaźniewicz-Łada M, Luczak M, Główka F. Pharmacokinetic studies of enantiomers of ibuprofen and its chiral metabolites in humans with different variants of genes coding CYP2C8 and CYP2C9 isoenzymes. Xenobiotica. 2009;39(6):476-85. DOI:10.1080/00498250902862705
12. López-Rodríguez R, Novalbos J, Gallego-Sandín S, et al. Influence of CYP2C8 and CYP2C9 polymorphisms on pharmacokinetic and pharmacodynamic parameters of racemic and enantiomeric forms of ibuprofen in healthy volunteers. Pharmacol Res. 2008;58(1):77-84. DOI:10.1016/j.phrs.2008.07.004
13. García-Martín E, Martínez C, Tabarés B, et al. Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin Pharmacol Ther. 2004;76(2):119-27. DOI:10.1016/j.clpt.2004.04.006
14. Kirchheiner J, Meineke I, Freytag G, et al. Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on the inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther. 2002;72(1):62-75. DOI:10.1067/mcp.2002.125726
15. Martínez C, García-Martín E, Blanco G, et al. The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. Br J Clin Pharmacol. 2005;59(1):62-9. DOI:10.1111/j.1365-2125.2004.02183.x
16. Dorado P, Cavaco I, Cáceres MC, et al. A. Relationship between CYP2C8 genotypes and diclofenac 5-hydroxylation in healthy Spanish volunteers. Eur J Clin Pharmacol. 2008;64(10):967-70.
DOI:10.1007/s00228-008-0508-4
17. Lazarska KE, Dekker SJ, Vermeulen NPE, Commandeur JNM. Effect of UGT2B7*2 and CYP2C8*4 polymorphisms on diclofenac metabolism. Toxicol Lett. 2018;284:70-8. DOI:10.1016/j.toxlet.2017.11.038
18. Daly AK, Aithal GP, Leathart JB, et al. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology. 2007;132(1):272-81. DOI:10.1053/j.gastro.2006.11.023
19. Cao L, Zhang Z, Sun W, et al. Impacts of COX-1 gene polymorphisms on vascular outcomes in patients with ischemic stroke and treated with aspirin. Gene. 2014;546(2):172-6. DOI:10.1016/j.gene.2014.06.023
20. Sharma V, Kaul S, Al-Hazzani A, et al. Association of COX-2 rs20417 with aspirin resistance. J Thromb Thrombolysis. 2013;35(1):95-9. DOI:10.1007/s11239-012-0777-8
21. Lee YS, Kim H, Wu TX, et al. Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs. Clin Pharmacol Ther. 2006;79(5):407-18. DOI:10.1016/j.clpt.2006.01.013
22. Caciagli L, Bulayeva K, Bulayev O, et al. The key role of patrilineal inheritance in shaping the genetic variation of Dagestan highlanders. J Hum Genet. 2009;54(12):689-94. DOI:10.1038/jhg.2009.94
23. Yunusbayev B, Metspalu M, Järve M, et al. The Caucasus as an asymmetric semipermeable barrier to ancient human migrations. Mol Biol Evol. 2012;29(1):359-65. DOI:10.1093/molbev/msr221
24. Mirzaev KB, Fedorinov DS, Ivashchenko DV, Sychev DA. ADME pharmacogenetics: future outlook for Russia. Pharmacogenomics. 2019;20(11):847-65. DOI:10.2217/pgs-2019-0013
25. Ромодановский Д.П., Хапаев Б.А., Игнатьев И.В., и др. Частоты «медленных» аллельных вариантов генов, кодирующих изоферменты цитохрома Р450 CYP2D6, CYP2C19, CYP2C9 у карачаевцев и черкесов. Биомедицина. 2010;1(2):33-7 [Romodanovskij DP, Hapaev BA, Ignatev IV, et al. Frequencies of “slow” allelic variants of genes encoding cytochrome P450 isoenzymes CYP2D6, CYP2C19, CYP2C9 in Karachais and Circassians. Biomedicine. 2010;1(2):33-7 (in Russian)].
26. Батурин В.А., Царукян А.А., Колодийчук Е.В. Исследование полиморфизма гена CYP2C9 в этнических группах населения Ставропольского края. Медицинский вестник Северного Кавказа. 2014;9(1):45-8 [Baturin VA, Carukyan AA, Kolodijchuk EV. Study of CYP2C9 gene polymorphism in ethnic groups of Stavropol Krai. Medical Bulletin of the North Caucasus. 2014;9(1):45-8 (in Russian)]. DOI:10.14300/mnnc.2014.09013
27. Sychev DA, Abdullaev SP, Mirzaev KB, et al. Genetic determinants of dabigatran safety (CES1 gene rs2244613 polymorphism) in the Russian population: multi-ethnic analysis. Mol Biol Rep. 2019;46(3):2761-69. DOI:10.1007/s11033-019-04722-w
28. Mirzaev KB, Sychev DA, Ryzhikova KA, et al. Genetic Polymorphisms of Cytochrome P450 Enzymes and Transport Proteins in a Russian Population and Three Ethnic Groups of Dagestan. Genet Test Mol Biomarkers. 2017;21(12):747-53. DOI:10.1089/gtmb.2017.0036
29. Tang H, Quertermous T, Rodriguez B, et al. Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies. Am J Hum Genet. 2005;76(2):268-75. DOI:10.1086/427888
30. The ALlele FREquency Database. Available at: https://alfred.med.yale.edu/alfred/index.asp. Accessed: 10.05.2021.
31. GnomAD Exome. Available at: https://gnomad.broadinstitute.org/ Accessed: 10.05.2021.
32. Karafet TM, Bulayeva KB, Bulayev OA, et al. Extensive genome-wide autozygosity in the population isolates of Daghestan. Eur J Hum Genet. 2015;23(10):1405-12. DOI:10.1038/ejhg.2014.299
________________________________________________
1. Onder G, Pellicciotti F, Gambassi G, Bernabei R. NSAID-related psychiatric adverse events: who is at risk? Drugs. 2004;64(23):2619‑27. DOI:10.2165/00003495-200464230-00001
2. Ghlichloo I, Gerriets V. Nonsteroidal Anti-inflammatory Drugs (NSAIDs). 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK547742/ Accessed: 04.05.2021.
3. Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging Dis. 2018;9(1):143-50. DOI:10.14336/AD.2017.0306
4. Karateev AE, Nasonov EL, Ivashkin VT, et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical guidelines. Rheumatology Science and Practice. 2018;56:1-29 (in Russian). DOI:10.14412/1995-4484-2018-1-29
5. Agúndez JA, García-Martín E, Martínez C. Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert Opin Drug Metab Toxicol. 2009;5(6):607-20. DOI:10.1517/17425250902970998
6. Zhou SF, Zhou ZW, Huang M. Polymorphisms of human cytochrome P450 2C9 and the functional relevance. Toxicology. 2010;278(2):165‑88. DOI:10.1016/j.tox.2009.08.013
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Авторы
Ш.П. Абдуллаев*1, Н.П. Денисенко1, К.Б. Мирзаев1, Г.Н. Шуев1, Ж.А. Созаева1, А.А. Качанова1, С.Н. Маммаев2, Э.А. Касаева2, Д.М. Гафуров3, Е.А. Гришина1, Д.А. Сычев1
1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Дагестанский государственный медицинский университет» Минздрава России, Махачкала, Россия;
3 ГБУ Республики Дагестан «Республиканский кардиологический диспансер», Махачкала, Россия
*abdullaevsp@gmail.com
1 ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия;
2 ФГБОУ ВО «Дагестанский государственный медицинский университет» Минздрава России, Махачкала, Россия;
3 ГБУ Республики Дагестан «Республиканский кардиологический диспансер», Махачкала, Россия
*abdullaevsp@gmail.com
________________________________________________
Sherzod P. Abdullaev*1, Natalia P. Denisenko1, Karin B. Mirzaev1, Gregorii N. Shuev1, Zhannet A. Sozaeva1, Anastasia A. Kachanova1, Suleiman N. Mammaev2, Elvira A. Kasaeva2, Danial M. Gafurov3, Elena A. Grishina1, Dmitry A. Sychev1
1 Russian Medical Academy of Continuous Professional Education, Moscow, Russia;
2 Dagestan State Medical University, Makhachkala, Russia;
3 Republican Cardiological Dispensary, Makhachkala, Russia
*abdullaevsp@gmail.com
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.