/ POVEZANOST GST POLIMORFIZAMA SA BIOMARKERIMA INFLAMACIJE I MULTI-ORGANSKOG OŠTEĆENJA U COVID-19

  • Djurdja Jerotić
  • Ana Krunić
Ključne reči: COVID-19, oksidativni stres, glutation S-transferaze, polimorfizam

Sažetak


Uvod: Imajući u vidu značajnu ulogu koju oksidativni stres ima u patofiziologiji COVID-19, može se pretpostaviti da razlike u kliničkim manifestacijama kod ovih pacijenata mogu biti posledica varijacija u genima koji kodiraju antioksidantne enzime, kao što su glutathione S-transferase (GST).

Cilj: Cilj ove studije bio je da se ispita povezanost polimorfizama citosolnih GST (GSTA1 rs3957357, GSTM3 rs1332018 i GSTP1 rs1695) sa pokazateljima zapaljenja (leukociti, limfociti, monociti, CRP, fibrinogen, feritin) i biomarkerima multiorganskog oštećenja (urea, kreatinin, AST, ALT, LDH) kod COVID-19 pacijenata u dva vremena.

Materijali i metode: Polimorfizmi GSTM3, GSTA1 i GSTP1 gena su određenii kod 150 COVID-19 pacijenata odgovarajućim PCR metodama. 

Rezultati: Pokazatelji zapaljenja (leukociti, limfociti, monociti) su porasli 7 dana po prijemu u bolnicu (p<0,001), dok su CRP i fibrinogen bili smanjeni (p<0,001). Od pet analiziranih biomarkera multiorganskog oštećenja, samo urea se značajno povećala 7 dana po prijemu (p<0,007), dok je AST pokazao statistički značajan pad (p<0,001). Pacijenti sa COVID-19 homozigoti za varijantni GSTM3*C/C genotip imali su povećane nivoe inflamatornih biomarkera kao što su CRP, fibrinogen i feritin, ali je granična značajnost pokazana samo za fibrinogen (p=0,057). Pacijenti sa COVID-19 homozigoti za varijantni GSTM3*C alel imali su najviše nivoe ALT (p=0,021) i LDH (p=0,045) po prijemu. 

Zaključak: Naši rezultati o povezanosti GSTM3 varijantnog genotipa sa pokazateljima sistemske inflamacije i oštećenja jetre kod pacijenata sa COVID-19 mogu doprineti daljem razumevanju patofizioloških mehanizama koji su u osnovi ove bolesti, kao i ranom prepoznavanju pacijenata sa COVID-19 sklonim pogoršanju toka bolesti.  

Reference


  1. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020;215:108427.

  2. Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D. Inflammation triggered by SARS-CoV-2 and ACE2 augment drives multiple organ failure of severe COVID-19: molecular mechanisms and implications. Inflammation. 2021;44(1):13–34.

  3. Joly BS, Siguret V, Veyradier A. Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Med. 2020;46(8):1603–6.

  4. Gibson PG, Qin L, Puah SH. COVID‐19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre‐COVID‐19 ARDS. Med J Aust. 2020;213(2):54–6.

  5. Fernandes IG, De Brito CA, Dos Reis VMS, Sato MN, Pereira NZ. SARS-CoV-2 and other respiratory viruses: What does oxidative Stress have to do with it? Oxid Med Cell Longev. 2020;2020.

  6. Miripour ZS, Sarrami-Forooshani R, Sanati H, Makarem J, Taheri MS, Shojaeian F, et al. Real-time diagnosis of reactive oxygen species (ROS) in fresh sputum by electrochemical tracing; correlation between COVID-19 and viral-induced ROS in lung/respiratory epithelium during this pandemic. Biosens Bioelectron. 2020;165:112435.

  7. Kosanovic T, Sagic D, Djukic V, Pljesa-Ercegovac M, Savic-Radojevic A, Bukumiric Z, et al. Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings. Antioxidants. 2021;10(7):1126.

  8. Muhammad Y, Kani YA, Iliya S, Muhammad JB, Binji A, El-Fulaty Ahmad A, et al. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE open Med. 2021;9:2050312121991246.

  9. Tew KD, Townsend DM. Glutathione-s-transferases as determinants of cell survival and death. Antioxid Redox Signal. 2012;17(12):1728–37.

  10. Menon D, Innes A, Oakley AJ, Dahlstrom JE, Jensen LM, Brüstle A, et al. GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity. Sci Rep. 2017;7(1):1–15.

  11. Pljesa-Ercegovac M, Savic-Radojevic A, Matic M, Coric V, Djukic T, Radic T, et al. Glutathione transferases: potential targets to overcome chemoresistance in solid tumors. Int J Mol Sci. 2018;19(12):3785.

  12. Saadat M. The morbidity and mortality of COVID-19 are correlated with the Ile105Val glutathione S-transferase P1 polymorphism. Egypt J Med Hum Genet. 2020;21(1):1–5.

  13. Abbas M, Verma S, Verma S, Siddiqui S, Khan FH, Raza ST, et al. Association of GSTM1 and GSTT1 gene polymorphisms with COVID‐19 susceptibility and its outcome. J Med Virol. 2021

  14. Coric V, Milosevic I, Djukic T, Bukumiric Z, Savic-Radojevic A, Matic M, et al. GSTP1 and GSTM3 variant alleles affect susceptibility and severity of COVID-19. Front Mol Biosci. :1169.

  15. Ali-Osman F, Akande O, Antoun G, Mao J-X, Buolamwini J. Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants: evidence for differential catalytic activity of the encoded proteins. J Biol Chem. 1997;272(15):10004–12.

  16. Di Pietro G, Magno LA V, Rios-Santos F. Glutathione S-transferases: an overview in cancer research. Expert Opin Drug Metab Toxicol. 2010;6(2):153–70.

  17. Tabary M, Khanmohammadi S, Araghi F, Dadkhahfar S, Tavangar SM. Pathologic features of COVID-19: A concise review. Pathol Pract. 2020;153097.

  18. Astuti I. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr Clin Res Rev. 2020;14(4):407–12.

  19. Mokhtari T, Hassani F, Ghaffari N, Ebrahimi B, Yarahmadi A, Hassanzadeh G. COVID-19 and multiorgan failure: A narrative review on potential mechanisms. J Mol Histol. 2020;1–16.

  20. Saadat M. An evidence for correlation between the glutathione S-transferase T1 (GSTT1) polymorphism and outcome of COVID-19. Clin Chim Acta. 2020;508:213.

  21. Thyagaraju K, Hemavathi B, Vasundhara K, Rao AD, Devi KN. Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene. J Zhejiang Univ Sci B. 2005;6(8):759–69.

  22. Wang S, Yang J, You L, Dai M, Zhao Y. GSTM3 Function and Polymorphism in Cancer: Emerging but Promising. Cancer Manag Res. 2020;12:10377.

  23. Flamant C, Henrion-Caude A, Boëlle P-Y, Brémont F, Brouard J, Delaisi B, et al. Glutathione-S-transferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis. Pharmacogenet Genomics. 2004;14(5):295–301.

  24. Çalışkan M, Baker SW, Gilad Y, Ober C. Host genetic variation influences gene expression response to rhinovirus infection. PLoS Genet. 2015;11(4):e1005111.

  25. van de Wetering C, Elko E, Berg M, Schiffers CHJ, Stylianidis V, van den Berge M, et al. Glutathione S-transferases and their implications in the lung diseases asthma and chronic obstructive pulmonary disease: Early life susceptibility? Redox Biol. 2021;101995.

  26. Qi L, Zou Z-Q, Wang L-Y, Gao S, Fan Y-C, Long B, et al. Methylation of the glutathione-S-transferase M3 gene promoter is associated with oxidative stress in acute-on-chronic hepatitis B liver failure. Tohoku J Exp Med. 2012;228(1):43–51.

Objavljeno
2023/05/18
Rubrika
Originalni naučni članak