Covid-19: Moleküler ve Klinik Yaklaşım

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DOI :10.26650/BB/CH22.2020.008.06   IUP :10.26650/BB/CH22.2020.008.06    Tam Metin (PDF)

COVID-19 Salgınında Anjiyotensin Dönüştürücü Enzim 2 Reseptörü Gen Varyantlarının Önemi

Ayşe Evrim Bayrak

Günümüzde halen mücadele edilen ve gelecekte olması beklenen koronavirüs kaynaklı şiddetli akut solunum yolu sendromları (SARS) nedeniyle ortaya çıkan salgınlara karşı, sürdürülebilir önleyici yaklaşımlar ve etkili tedavi protokollerinin geliştirilmesi gerekmektedir. SARS-CoV-2 virüs enfeksiyonu nedeni ile meydana gelen koronavirüs hastalığı-2019 (COVID-19) salgını halen devam ederken yüksek riskli bireylerin erken tanısında prognostik belirteçlerin belirlenmesi acil bir ihtiyaç olarak görülmektedir. Bu süreçte, bireysel ve toplumsal farklılıkları belirlemek için kapsamlı genetik analizlere ve antijen işleme/sunma yolaklarını açıklayacak araştırmalara hız verilmiştir. Koronavirüslerin konakçı hücrelere giriş noktalarındaki reseptörlerden biri olan Anjiyotensin Dönüştürücü Enzim-2 (ACE2), esas olarak sistemik kan basıncını düzenleyen renin anjiyotensin aldosteron sisteminde (RAAS), anjiotensinojen I’in anjiotensin (1-7)’ye dönüşmesini sağlayan ve anjiyotensin I’i anjiyotensin II’ye dönüştüren ACE ile yüksek homoloji gösteren bir tip I transmembran metallokarboksipeptidaz olarak bilinmektedir. Kronik hastalıklarda, ACE2 genindeki varyantların ve ifade edildiği hücrelerdeki düzeylerin ilişkilerini araştıran çok sayıda çalışma mevcuttur. Son aylarda yapılan çalışmalarda, diyabet ve hipertansiyon gibi komorbiditelere genetik yatkınlıkta ve bunların tedavi uygulamalarında aynı zamanda SARS-CoV-2 enfeksiyonunda virüsün S (başak, ing. “Spike”) glikoproteini ile etkileşmesinde, ACE2 genindeki fonksiyonel varyantlar ve olası etkileri araştırılmaktadır. Bu derlemede, özellikle küresel salgın döneminde ACE2 gen varyantları ile ilgili farklı toplumlarda yapılmış araştırmalar özetlenmektedir.


Anahtar Kelimeler: SARS-CoV-2, COVID-19, ACE2 reseptörü, gen varyantları
DOI :10.26650/BB/CH22.2020.008.06   IUP :10.26650/BB/CH22.2020.008.06    Tam Metin (PDF)

The Importance of Angiotensin-Converting Enzyme 2 Receptor Gene Variants in COVID-19 Pandemia

Ayşe Evrim Bayrak

Sustainable prevention and effective treatment approaches need to be developed against outbreaks caused by severe acute respiratory syndromes (SARS) based on coronavirus, which we still struggle with and expect to see in the future. While the outbreak of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus infection still continues, the determination of prognostic markers in the early diagnosis appears to be an urgent need for high-risk individuals. In this process, comprehensive genetic analysis and research to explain antigen processing/presentation pathways were accelerated to identify individual and social differences. Angiotensin-Converting Enzyme-2 (ACE2), one of the receptors at the entry point of the coronaviruses to host cells, is used mainly in the system of renin angiotensin aldosterone (RAAS), which regulates the angiotensinogen II into angiotensin 1-7. It is known as a type I transmembrane metallocarboxypeptidase, which shows high homology with ACE that converts angiotensin I to angiotensin II. There are many studies investigating the relationship between ACE2 gene variants and ACE2 expression levels in chronic diseases. In recent studies, functional variants in the ACE2 gene and their possible effects are investigated in genetic susceptibility to comorbidities such as diabetes and hypertension, in treatment applications of comorbidities and in the interaction of the virus with the Spike glycoprotein in the SARS-CoV-2 infection. This review summarizes the studies conducted in different populations related to ACE2 gene variants, especially during the pandemic period.


Anahtar Kelimeler: SARS-CoV-2, COVID-19, ACE2 receptor, gene variants

Referanslar

  • 1. Darbani B. The Expression and Polymorphism of Entry Machinery for COVID-19 in Human: Juxtaposing Population Groups, Gender, and Different Tissues. Int J Environ Res Public Health. 2020; 17(10): 3433. doi: 10.3390/ijerph17103433 google scholar
  • 2. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003; 300(5624): 1394-9. google scholar
  • 3. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270-3. google scholar
  • 4. Devaux CA, Rolain JM, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect. 2020; 53(3): 425-35. google scholar
  • 5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497-506. google scholar
  • 6. Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, et al. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020; 39(10): e105114. doi: 10.15252/ embj.20105114 google scholar
  • 7. Asselta R, Paraboschi EM, Mantovani A, Duga S. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging (Albany NY). 2020; 12(11): 10087-98. google scholar
  • 8. Bwire GM. Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women? SN Compr Clin Med. 2020:1-3. doi: 10.1007/s42399-020-00341-w google scholar
  • 9. De La Vega R, Barquín RR, Boros S, Szabo A. Could attitudes toward COVID-19 in Spain render men more vulnerable than women? PsyArXiv Prepr. 2020. https://doi.org/10.31234/osf.io/dyxqn google scholar
  • 10. Chaoxin J, Daili S, Yanxin H, Ruwei G, Chenlong W, Yaobin T. The influence of angiotensin-converting enzyme 2 gene polymorphisms on type 2 diabetes mellitus and coronary heart disease. Eur Rev Med Pharmacol Sci. 2013; 17(19): 2654-9. google scholar
  • 11. Patel SK, Wai B, Ord M, MacIsaac RJ, Grant S, Velkoska E, et al. Association of ACE2 genetic variants with blood pressure, left ventricular mass, and cardiac function in Caucasians with type 2 diabetes. Am J Hypertens. 2012; 25(2): 216-22. google scholar
  • 12. Yang W, Huang W, Su S, Li B, Zhao W, Chen S, Gu D. Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population. Clin Sci (Lond). 2000; 111(5): 333-40. google scholar
  • 13. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13): 1239-42. google scholar
  • 14. Simmons G, Zmora P, Gierer S, Heurich A, Pöhlmann S. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research. Version 2. Antiviral Res. 2013; 100(3): 605-14. google scholar
  • 15. Matsuyama S, Ujike M, Morikawa S, Tashiro M, Taguchi F. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc Natl Acad Sci U S A. 2005; 102(35): 12543-7. google scholar
  • 16. Wang H, Yang P, Liu K, Guo F, Zhang Y, Zhang G, Jiang C. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res. 2008; 18(2): 290-301. google scholar
  • 17. White JM, Whittaker GR. Fusion of Enveloped Viruses in Endosomes. Traffic. 2016; 17(6): 593-614. google scholar
  • 18. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203(2): 631-7. google scholar
  • 19. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2): 271-80. google scholar
  • 20. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020; 181(2): 281-92. google scholar
  • 21. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020; 367(6485): 1444-8. 64 COVID-19 Salgınında Anjiyotensin Dönüştürücü Enzim 2 Reseptörü Gen Varyantlarının Önemi google scholar
  • 22. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020; 14(2): 185-92. google scholar
  • 23. Gallagher TM, Buchmeier MJ. Coronavirus spike proteins in viral entry and pathogenesis. Virology. 2001; 279(2): 371-4. google scholar
  • 24. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965): 450-4. google scholar
  • 25. Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol. 2012; 86(12): 6537-45. google scholar
  • 26. Burkard C, Verheije MH, Wicht O, van Kasteren SI, van Kuppeveld FJ, Haagmans BL, et al. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner. PLoS Pathog. 2014; 10(11): e1004502. doi: 10.1371/journal.ppat.1004502 google scholar
  • 27. Millet JK, Whittaker GR. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furinmediated activation of the spike protein. Proc Natl Acad Sci U S A. 2014; 111(42): 15214-9. google scholar
  • 28. Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005; 24(8): 1634-43. google scholar
  • 29. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. A novel angiotensin- converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000; 87(5): E1-9. doi: 10.1161/01.res.87.5.e1 google scholar
  • 30. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000; 275(43): 33238-43. google scholar
  • 31. Tukiainen T, Villani AC, Yen A, Rivas MA, Marshall JL, Satija R, et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017; 550: 244. google scholar
  • 32. Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ, et al. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res. 2020; 126(10): 1456-74. google scholar
  • 33. Wysocki J, Ye M, Soler MJ, Gurley SB, Xiao HD, Bernstein KE, et al. ACE and ACE2 activity in diabetic mice. Diabetes. 2006; 55(7): 2132-9. google scholar
  • 34. Yamamoto K, Ohishi M, Katsuya T, Ito N, Ikushima M, Kaibe M, et al. Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II. Hypertension. 2006; 47(4): 718-26. google scholar
  • 35. Rabelo LA, Todiras M, Nunes-Souza V, Qadri F, Szijártó IA, Gollasch M, Penninger JM, et al. Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress. PLoS One. 2016; 11(4): e0150255. doi: 10.1371/journal.pone.0150255 google scholar
  • 36. Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X, et al. Comparative genetic analysis of the novel coronavirus (2019- nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020; 6: 11. doi: 10.1038/s41421-020- 0147-1. google scholar
  • 37. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single- cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv. 2020. https://doi.org/10.1101/2020.01.26.919985 google scholar
  • 38. Cai G, Bossé Y, Xiao F, Kheradmand F, Amos CI. Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020; 201(12): 1557-9. google scholar
  • 39. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020; 382(18): 1708-20. google scholar
  • 40. Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv 2020.01.30.927806. doi: https:// doi.org/10.1101/2020.01.30.927806 google scholar
  • 41. Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020; 12(1): 8. doi: 10.1038/s41368-020-0074-x Kömürcü-Bayrak 65 google scholar
  • 42. Chai X, Hu L , Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv 2020.02.03.931766. doi: https://doi.org/10.1101/2020.02.03.931766 google scholar
  • 43. Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020; 181(5): 1016-35.e19. google scholar
  • 44. de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016; 14(8): 523-34. google scholar
  • 45. Nicin L, Abplanalp WT, Mellentin H, Kattih B, Tombor L, John D, et al. Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. Eur Heart J. 2020; 41(19): 1804-6. google scholar


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