Drug-disease interactions of differentially expressed genes in COVID-19 liver samples: an in-silico analysis
Interacciones fármaco–enfermedad de genes diferencialmente expresados en muestras de hígado de COVID-19: un análisis in-silico.
Palabras clave:
COVID-19, hígado, citocromo P450, expresión génica
Resumen
Mientras que se han informado sobre lesiones hepáticas por COVID-19 en diversos estudios, las preocupaciones se elevan acerca de las reacciones enfermedad-fármaco en los pacientes con COVID-19. En este estudio, investigamos la hipótesis de las interacciones gen-enfermedad en un modelo in-silico de la expresión génica para buscar los cambios en los genes del citocromo P450. En este estudio se utilizó el conjunto de datos Ómnibus de la Expresión Génica de la autopsia hepática en los pacientes fallecidos por COVID-19 (GSE150316). Las biopsias de hígado graso no alcohólico se utilizaron como controles (GSE167523). Además, el análisis de la expresión génica se realizó mediante el método DESeq / EdgeR. Se utilizaron las bases de datos GO y las rutas fueron ajustadas en p <0,05. La base de datos de la interacción fármaco-gen (DGIdb) fue investigada para las interacciones. Según los resultados, 5.147 genes se regularon a la baja y 5.122 genes se regularon al alza en el SARS-CoV-2 en comparación con los hígados sanos. En comparación con los citocromos, 34 citocromos se regularon a la baja, mientras que 4 citocromos fueron regulados al alza entre la expresión de los genes detectados diferencialmente (DEG). La base de datos de la interacción fármaco-gen (DGIdb) proporcionó una lista de medicamentos con las interacciones potenciales con COVID-19, así como con metacetamol, fenetilo isocianato, amodiaquina, espironolactona, amilorida, acenocumarol, clopidogrel, fenprocoumon, trimipramina, fenazepam, etc. También, los compuestos dietéticos de isoflavonas, valeriana y cumarina, así como el metabolismo de la cafeína han mostrado tener posibles interacciones con la enfermedad COVID-19. Nuestro estudio demostró que los niveles de la expresión de los genes del citocromo P450 podrían quedar alterados siguiendo COVID-19. Además, se recomienda utilizar una lista de fármaco-enfermedad interacción para evaluar en las consideraciones clínicas en otros estudios adicionales.
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Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol 2020:5(5):428- 430.
Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y. Characteristics of Liver Tests in COVID-19 Patients. J Hepatol 2020.
Afra HS, Amiri-Dashatan N, Ghorbani F, Maleki I, Rezaei-Tavirani M. Positive association between severity of COVID-19 infection and liver damage: a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench 2020;13(4):292.
Wang Y, Liu S, Liu H, Li W, Lin F, Jiang L, Li X, Xu P, Zhang L, Zhao L, Cao Y. SARS- CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol 2020:73(4):807-816.
Alqahtani SA, Schattenberg JM. Liver injury in COVID-19: The current evidence. United European Gastroenterol J 2020: 8(5):509-519.
Gurala D, Al Moussawi H, Philipose J, Abergel JR. Acute liver failure in a COVID-19 patient without any preexisting liver disease. Cureus 2020:12(8).
El-Ghiaty MA, Shoieb SM, El-Kadi AO. Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms. Med Hypotheses 2020;144:110033.
Guengerich FP, Wilkey CJ, Phan TT. Human cytochrome P450 enzymes bind drugs and other substrates mainly through conformational-selection modes. J Biol Chem 2019:294(28):10928-41.
Ge SX, Son EW, Yao R. iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC bioinform 2018:19(1):534.
Harrelson JP, Stamper BD, Chapman JD, Goodlett DR, Nelson SD. Covalent modification and time-dependent inhibition of human CYP2E1 by the meta-isomer of acetaminophen. Drug Metab Dispos 2012:40(8):1460-1465.
Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005:77(5):415- 426.
Obraztsov VV, AIu G, Shekhtman DG, Sklifas AN, Makarov KN. Interaction of perfluoroctylbromide with liver microsomal monooxygenase. Biokhimiia (Moscow, Russia) 1993:58(8):1234-1239.
Yoshigae Y, Sridar C, Kent UM, Hollenberg PF. The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation. Drug Metab Dispos 2013:41(4):858-869.
Mazurov AA, Kombo DC, Hauser TA, Miao L, Dull G, Genus JF, Fedorov NB, Benson L, Sidach S, Xiao Y, Hammond PS. Discovery of (2 S, 3 R)-N-[2-(Pyridin-3-ylmethyl)- 1-azabicyclo [2.2. 2] oct-3-yl] benzo [b] furan-2-carboxamide (TC-5619), a selective α7 nicotinic acetylcholine receptor agonist, for the treatment of cognitive disorders. J Med Chem 2012:55(22):9793-9809.
Kishida T, Nagamoto M, Ohtsu Y, Watakabe M, Ohshima D, Nashiki K, Mizushige T, Izumi T, Obata A, Ebihara K. Lack of an inducible effect of dietary soy isoflavones on the mRNA abundance of hepatic cytochrome P-450 isozymes in rats. Biosci Biotechnol Biochem 2004:68(3):508-515.
Parikh S, Ouedraogo JB, Goldstein JA, Rosenthal PJ, Kroetz DL. Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther 2007:82(2):197-203.
Gil JP. Amodiaquine pharmacogenetics. Pharmacogenomics 2008:9(10):1385-90.
Ishikawa C, Ozaki H, Nakajima T, Ishii T, Kanai S, Anjo S, Shirai K, Inoue I. A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin. J Hum Genet 2004:49(10):582-585.
Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002:346(7):539-540.
Meunier V, Bourrie M, Julian B, Marti E, Guillou F, Berger Y, Fabre G. Expression and induction of CYP1A1/1A2, CYP2A6 and CYP3A4 in primary cultures of human hepatocytes: a 10-year follow-up. Xenobiotica 2000:30(6):589-607.
Malaiyandi V, Lerman C, Benowitz NL, Jepson C, Patterson F, Tyndale RF. Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Mol Psychiatry 2006:11(4):400-409.
Pitarque M, von Richter O, Oke B, Berkkan H, Oscarson M, Ingelman-Sundberg M. Identification of a single nucleotide polymorphism in the TATA box of the CYP2A6 gene: impairment of its promoter activity. Biochem Biophys Res Commun 2001:284(2):455-460.
Tani N, Juvonen RO, Raunio H, Fashe M, Leppänen J, Zhao B, Tyndale RF, Rahnasto-Rilla M. Rational design of novel CYP2A6 inhibitors. Bioorg Med Chem 2014:22(23):6655-6664.
Pearce RE, Vakkalagadda GR, Leeder JS. Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2-and 3-hydroxylated metabolites. Drug Metab Dispos 2002:30(11):1170-1179.
Wypasek E, Branicka A, Awsiuk M, Sadowski J, Undas A. Genetic determinants of ace nocoumarol and warfarin maintenance dose requirements in Slavic population: a potential role of CYP4F2 and GGCX polymorphisms. Thromb Res 2014:134(3):604-609.
Kupstyte N, Zaliunas R, Tatarunas V, Skipskis V, Zaliaduonyte-Peksiene D, Grabauskyte I, Dovidaitiene D, Bumblauskas K, Gustiene O, Lesauskaite V. Effect of clinical factors and gene polymorphism of CYP2C19* 2,* 17 and CYP4F2* 3 on early stent thrombosis. Pharmacogenomics 2015:16(3):181-189.
van Schie RM, Aoussar A, van der Meer FJ, De Boer A, Maitland-van der Zee AH. Evaluation of the effects of single-nucleotide polymorphisms in CYP3A4 and CYP4F2 on stable phenprocoumon and acenocoumarol maintenance doses. J Thromb Haemost 2013:11(6):1200-3.
Deeken JF, Cormier T, Price DK, Sissung TM, Steinberg SM, Tran K, Liewehr DJ, Dahut WL, Miao X, Figg WD. A pharmacogenetic study of docetaxel and thalidomide in patients with castration-
resistant prostate cancer using the DMET genotyping platform. Pharmacogenomics J 2010:10(3):191-199.
Tsambaos D, Bolsen K, Georgiou S, Monastirli A, Goerz G. Effects of oral thalidomide on rat liver and skin microsomal P450 isozyme activities and on urinary porphyrin excretion: interaction with oral hexachlorobenzene. Arch Dermatol Res 1994:286(6):347-349.
Marez D, Sabbagh N, Legrand M, Lo-Guidice JM, Boone P, Broly F. A novel CYP2D6 allele with an abolished splice recognition site associated with the poor metabolizer phenotype. Pharmacogenetics 1995: 5(5):305-311.
Cusato J, Allegra S, De Nicolò A, Boglione L, Fatiguso G, Abdi AM, Cariti G, Di Perri G, D’Avolio A. Intracellular and plasma trough concentration and pharmaco-genetics of telaprevir. J Pharm Pharm Sci 2015:18(2):171-6.
Allegra S, Cusato J, De Francia S, Arduino A, Longo F, Pirro E, Massano D, De Nicolò A, Piga A, D’avolio A. Role of CYP24A1, VDR and GC gene polymorphisms on deferasirox pharmacokinetics and clinical outcomes. Pharmacogenomics J 2018:18(3):506-515.
Ferla S, Aboraia AS, Brancale A, Pepper CJ, Zhu J, Ochalek JT, DeLuca HF, Simons C. Small-molecule inhibitors of 25-hydro- xyvitamin D-24-hydroxylase (CYP24A1): synthesis and biological evaluation. J Med Chem 2014: 57(18):7702-7715.
Relats C, Sadeghi-Reeves L, Zbären E, Jenzer H. The role of food-drug-cytochrome P450 interactions in breast cancer. Med Sci Rev 2018: (5):25-34.
Hatami N, Ahi S, Sadeghinikoo A, Foroughian M, Javdani F, Kalani N, Fereydoni M, Keshavarz P. Worldwide ACE (I/D) polymorphism may affect COVID-19 recovery rate: an ecological meta-regression. Endocrine 2020; 68:479-484.
Parsa S, Mogharab V, Ebrahimi M, Ahmadi SR, Shahi B, Mehramiz NJ, Foroughian M, Zarenezhad M, Kalani N, Abdi MH, Javdani F. COVID-19 as a worldwide selective event and bitter taste receptor polymorphisms: An ecological correlational study. Int J Biol Macromol 2021;177:204-210.
Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, Li Z, Zhou G, Gou J, Qu J, Sun Y. Characteristics of Liver Tests in COVID-19 Patients. J Hepatol 2020.
Afra HS, Amiri-Dashatan N, Ghorbani F, Maleki I, Rezaei-Tavirani M. Positive association between severity of COVID-19 infection and liver damage: a systematic review and meta-analysis. Gastroenterol Hepatol Bed Bench 2020;13(4):292.
Wang Y, Liu S, Liu H, Li W, Lin F, Jiang L, Li X, Xu P, Zhang L, Zhao L, Cao Y. SARS- CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol 2020:73(4):807-816.
Alqahtani SA, Schattenberg JM. Liver injury in COVID-19: The current evidence. United European Gastroenterol J 2020: 8(5):509-519.
Gurala D, Al Moussawi H, Philipose J, Abergel JR. Acute liver failure in a COVID-19 patient without any preexisting liver disease. Cureus 2020:12(8).
El-Ghiaty MA, Shoieb SM, El-Kadi AO. Cytochrome P450-mediated drug interactions in COVID-19 patients: Current findings and possible mechanisms. Med Hypotheses 2020;144:110033.
Guengerich FP, Wilkey CJ, Phan TT. Human cytochrome P450 enzymes bind drugs and other substrates mainly through conformational-selection modes. J Biol Chem 2019:294(28):10928-41.
Ge SX, Son EW, Yao R. iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC bioinform 2018:19(1):534.
Harrelson JP, Stamper BD, Chapman JD, Goodlett DR, Nelson SD. Covalent modification and time-dependent inhibition of human CYP2E1 by the meta-isomer of acetaminophen. Drug Metab Dispos 2012:40(8):1460-1465.
Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005:77(5):415- 426.
Obraztsov VV, AIu G, Shekhtman DG, Sklifas AN, Makarov KN. Interaction of perfluoroctylbromide with liver microsomal monooxygenase. Biokhimiia (Moscow, Russia) 1993:58(8):1234-1239.
Yoshigae Y, Sridar C, Kent UM, Hollenberg PF. The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation. Drug Metab Dispos 2013:41(4):858-869.
Mazurov AA, Kombo DC, Hauser TA, Miao L, Dull G, Genus JF, Fedorov NB, Benson L, Sidach S, Xiao Y, Hammond PS. Discovery of (2 S, 3 R)-N-[2-(Pyridin-3-ylmethyl)- 1-azabicyclo [2.2. 2] oct-3-yl] benzo [b] furan-2-carboxamide (TC-5619), a selective α7 nicotinic acetylcholine receptor agonist, for the treatment of cognitive disorders. J Med Chem 2012:55(22):9793-9809.
Kishida T, Nagamoto M, Ohtsu Y, Watakabe M, Ohshima D, Nashiki K, Mizushige T, Izumi T, Obata A, Ebihara K. Lack of an inducible effect of dietary soy isoflavones on the mRNA abundance of hepatic cytochrome P-450 isozymes in rats. Biosci Biotechnol Biochem 2004:68(3):508-515.
Parikh S, Ouedraogo JB, Goldstein JA, Rosenthal PJ, Kroetz DL. Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther 2007:82(2):197-203.
Gil JP. Amodiaquine pharmacogenetics. Pharmacogenomics 2008:9(10):1385-90.
Ishikawa C, Ozaki H, Nakajima T, Ishii T, Kanai S, Anjo S, Shirai K, Inoue I. A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin. J Hum Genet 2004:49(10):582-585.
Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002:346(7):539-540.
Meunier V, Bourrie M, Julian B, Marti E, Guillou F, Berger Y, Fabre G. Expression and induction of CYP1A1/1A2, CYP2A6 and CYP3A4 in primary cultures of human hepatocytes: a 10-year follow-up. Xenobiotica 2000:30(6):589-607.
Malaiyandi V, Lerman C, Benowitz NL, Jepson C, Patterson F, Tyndale RF. Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Mol Psychiatry 2006:11(4):400-409.
Pitarque M, von Richter O, Oke B, Berkkan H, Oscarson M, Ingelman-Sundberg M. Identification of a single nucleotide polymorphism in the TATA box of the CYP2A6 gene: impairment of its promoter activity. Biochem Biophys Res Commun 2001:284(2):455-460.
Tani N, Juvonen RO, Raunio H, Fashe M, Leppänen J, Zhao B, Tyndale RF, Rahnasto-Rilla M. Rational design of novel CYP2A6 inhibitors. Bioorg Med Chem 2014:22(23):6655-6664.
Pearce RE, Vakkalagadda GR, Leeder JS. Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2-and 3-hydroxylated metabolites. Drug Metab Dispos 2002:30(11):1170-1179.
Wypasek E, Branicka A, Awsiuk M, Sadowski J, Undas A. Genetic determinants of ace nocoumarol and warfarin maintenance dose requirements in Slavic population: a potential role of CYP4F2 and GGCX polymorphisms. Thromb Res 2014:134(3):604-609.
Kupstyte N, Zaliunas R, Tatarunas V, Skipskis V, Zaliaduonyte-Peksiene D, Grabauskyte I, Dovidaitiene D, Bumblauskas K, Gustiene O, Lesauskaite V. Effect of clinical factors and gene polymorphism of CYP2C19* 2,* 17 and CYP4F2* 3 on early stent thrombosis. Pharmacogenomics 2015:16(3):181-189.
van Schie RM, Aoussar A, van der Meer FJ, De Boer A, Maitland-van der Zee AH. Evaluation of the effects of single-nucleotide polymorphisms in CYP3A4 and CYP4F2 on stable phenprocoumon and acenocoumarol maintenance doses. J Thromb Haemost 2013:11(6):1200-3.
Deeken JF, Cormier T, Price DK, Sissung TM, Steinberg SM, Tran K, Liewehr DJ, Dahut WL, Miao X, Figg WD. A pharmacogenetic study of docetaxel and thalidomide in patients with castration-
resistant prostate cancer using the DMET genotyping platform. Pharmacogenomics J 2010:10(3):191-199.
Tsambaos D, Bolsen K, Georgiou S, Monastirli A, Goerz G. Effects of oral thalidomide on rat liver and skin microsomal P450 isozyme activities and on urinary porphyrin excretion: interaction with oral hexachlorobenzene. Arch Dermatol Res 1994:286(6):347-349.
Marez D, Sabbagh N, Legrand M, Lo-Guidice JM, Boone P, Broly F. A novel CYP2D6 allele with an abolished splice recognition site associated with the poor metabolizer phenotype. Pharmacogenetics 1995: 5(5):305-311.
Cusato J, Allegra S, De Nicolò A, Boglione L, Fatiguso G, Abdi AM, Cariti G, Di Perri G, D’Avolio A. Intracellular and plasma trough concentration and pharmaco-genetics of telaprevir. J Pharm Pharm Sci 2015:18(2):171-6.
Allegra S, Cusato J, De Francia S, Arduino A, Longo F, Pirro E, Massano D, De Nicolò A, Piga A, D’avolio A. Role of CYP24A1, VDR and GC gene polymorphisms on deferasirox pharmacokinetics and clinical outcomes. Pharmacogenomics J 2018:18(3):506-515.
Ferla S, Aboraia AS, Brancale A, Pepper CJ, Zhu J, Ochalek JT, DeLuca HF, Simons C. Small-molecule inhibitors of 25-hydro- xyvitamin D-24-hydroxylase (CYP24A1): synthesis and biological evaluation. J Med Chem 2014: 57(18):7702-7715.
Relats C, Sadeghi-Reeves L, Zbären E, Jenzer H. The role of food-drug-cytochrome P450 interactions in breast cancer. Med Sci Rev 2018: (5):25-34.
Hatami N, Ahi S, Sadeghinikoo A, Foroughian M, Javdani F, Kalani N, Fereydoni M, Keshavarz P. Worldwide ACE (I/D) polymorphism may affect COVID-19 recovery rate: an ecological meta-regression. Endocrine 2020; 68:479-484.
Parsa S, Mogharab V, Ebrahimi M, Ahmadi SR, Shahi B, Mehramiz NJ, Foroughian M, Zarenezhad M, Kalani N, Abdi MH, Javdani F. COVID-19 as a worldwide selective event and bitter taste receptor polymorphisms: An ecological correlational study. Int J Biol Macromol 2021;177:204-210.
Publicado
2021-11-29
Cómo citar
Rasoo, S. O., Nah, A. M., Eskandar, S., Hosseinzadeh, M., Asoudeh Moghanloo, S., & Ebrahimzadeh, F. (2021). Drug-disease interactions of differentially expressed genes in COVID-19 liver samples: an in-silico analysis: Interacciones fármaco–enfermedad de genes diferencialmente expresados en muestras de hígado de COVID-19: un análisis in-silico. Investigación Clínica, 62(4), 316-324. https://doi.org/10.22209/IC.v62n4a03
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