CYP2C8, PTGS-1, 2 gene polymorphisms prevalence associated with sensitivity to non-steroidal anti-inflammatory drugs among North Caucasus ethnic groups
- Authors: Abdullaev S.P.1, Denisenko N.P.1, Mirzaev K.B.1, Shuev G.N.1, Sozaeva Z.A.1, Kachanova A.A.1, Mammaev S.N.2, Kasaeva E.A.2, Gafurov D.M.3, Grishina E.A.1, Sychev D.A.1
-
Affiliations:
- Russian Medical Academy of Continuous Professional Education
- Dagestan State Medical University
- Republican Cardiological Dispensary
- Issue: Vol 93, No 11 (2021)
- Pages: 1334-1339
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/99612
- DOI: https://doi.org/10.26442/00403660.2021.11.201220
- ID: 99612
Cite item
Full Text
Abstract
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.
Full Text
##article.viewOnOriginalSite##About the authors
Sherzod P. Abdullaev
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0001-9001-1499
канд. биол. наук, зав. отд. молекулярой медицины Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowNatalia P. Denisenko
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0003-3278-5941
канд. мед. наук, зав. отд. персонализированной медицины Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowKarin B. Mirzaev
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0002-9307-4994
канд. мед. наук, зав. лаб. Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowGregorii N. Shuev
Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0002-5031-0088
мл. науч. сотр. отд. персонализированной медицины Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowZhannet A. Sozaeva
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0001-5166-7903
мл. науч. сотр. отд. молекулярной медицины Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowAnastasia A. Kachanova
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0003-3194-4410
мл. науч. сотр. отд. молекулярной медицины Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowSuleiman N. Mammaev
Dagestan State Medical University
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0001-8898-8831
д-р мед. наук, проф., зав. каф. госпитальной терапии №1 ФГБОУ ВО ДГМУ
Russian Federation, MakhachkalaElvira A. Kasaeva
Dagestan State Medical University
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0003-0234-0597
канд. мед. наук, ассистент каф. госпитальной терапии №1, ФГБОУ ВО ДГМУ
Russian Federation, MakhachkalaDanial M. Gafurov
Republican Cardiological Dispensary
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0002-8321-9176
врач ГБУ РД РКД
Russian Federation, MakhachkalaElena A. Grishina
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0002-5621-8266
д-р биол. наук, доц., дир. Научно-исследовательского института молекулярной и персонализированной медицины ФГБОУ ДПО РМАНПО
Russian Federation, MoscowDmitry A. Sychev
Russian Medical Academy of Continuous Professional Education
Email: abdullaevsp@gmail.com
ORCID iD: 0000-0002-4496-3680
чл.-кор. РАН, проф. РАН, д-р мед. наук, проф., ректор ФГБОУ ДПО РМАНПО
Russian Federation, MoscowReferences
- 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
- Ghlichloo I, Gerriets V. Nonsteroidal Anti-inflammatory Drugs (NSAIDs). 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK547742/ Accessed: 04.05.2021.
- 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
- 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
- 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
- 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
- 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
- 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
- Davies NM, Anderson KE. Clinical pharmacokinetics of naproxen. Clin Pharmacokinet. 1997;32(4):268-93. doi: 10.2165/00003088-199732040-00002
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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)].
- 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
- 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
- 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
- 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
- The ALlele FREquency Database. Available at: https://alfred.med.yale.edu/alfred/index.asp. Accessed: 10.05.2021.
- GnomAD Exome. Available at: https://gnomad.broadinstitute.org/ Accessed: 10.05.2021.
- 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
![](/img/style/loading.gif)