Cancer patients with Angiotensin-converting enzyme (ACE) gene polymorphism and COVID-19 phenotypic expression predisposed to SARS-CoV-2 infection
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Abstract
Pathogenesis of COVID-19 has been linked to the Angiotensin system. Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus, serves as a cellular receptor for SARS-CoV-2, suggesting that a person's vulnerability to infection may be controlled by how much of the ACE2 gene is expressed. It is also possible that the severity of COVID-19 is related to the equilibrium between ACE1 and ACE2 activity, which has been linked to the etiology of respiratory disorders. This study aimed to investigate the association of ACE1 I/D polymorphism with the severity of Covid-19. The study looked at 113 people-(50 healthy controls, 63 people with Covid). Results for the ACE2 rs4240157 T > C polymorphism were obtained. Logistic regression was used to evaluate the distribution frequencies of variables across the study groups. The ACE1-CC*CT genotype (p = 0.049) and male gender (p0.001) were related to severe COVID-19. COVID-19 severity was found to be associated with the ACE2–CT genotype through multiple logistic regression under the co-dominant inheritance model: CC*CT Allele, 95% CI (0.0104 to 0.2954), Significance level, (0.0007) Odd Ratio (0.0556); CC*TT Allele, 95% CI (0.1854 to 6.1927), Significance level, (0.9386) Odd Ratio (1.0714); and CT*TT (19.2857). This was assuming the ACE2–CC*CT genotype was connected with covid-19 severity. However, the ACE2 polymorphism did not affect the development of illness. In conclusion, male gender, malignancy, and the ACE1 genotype were linked to a negative result of COVID-19. Our results indicated that ACE1-C/T might affect COVID-19 severity; however, this association was hypertensive status-specific. However, this finding needs to be confirmed in additional large samples.
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Article Details
ACE, COVID-19, ACE1, PCR, Gene polymorphisms, TETRA-ARMS
Karagiannidis, C., Mostert, C., Hentschker, C., Voshaar, T., Malzahn, J., Schillinger, G., ... & Busse, R. (2020). Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study. The Lancet Respiratory Medicine, 8(9), 853-862.
COVID, C. (19). global cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU).
Mondragon, A. (2020). An Exploration of Risk Communications and Perceptions on COVID-19 Pandemic in the United States: A Systematic Literature Review (Doctoral dissertation, California State University San Marcos).
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., ... & Pöhlmann, S. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. cell, 181(2), 271-280.
Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B. J., & Jiang, S. (2009). The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nature Reviews Microbiology, 7(3), 226-236.
Ko, C. J., Huang, C. C., Lin, H. Y., Juan, C. P., Lan, S. W., Shyu, H. Y., ... & Lee, M. S. (2015). Androgen-induced TMPRSS2 activates matriptase and promotes extracellular matrix degradation, prostate cancer cell invasion, tumor growth, and metastasis. Cancer Research, 75(14), 2949-2960.
Tang, Q., Wang, Y., Ou, L., Li, J., Zheng, K., Zhan, H., ... & Wang, X. (2021). Downregulation of ACE2 expression by SARS-CoV-2 worsens the prognosis of KIRC and KIRP patients via metabolism and immunoregulation. International Journal of Biological Sciences, 17(8), 1925.
McFadyen, J. D., Stevens, H., & Peter, K. (2020). The emerging threat of (micro) thrombosis in COVID-19 and its therapeutic implications. Circulation Research, 127(4), 571-587.
Verdecchia, P., Cavallini, C., Spanevello, A., & Angeli, F. (2020). The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. European Journal of Internal Medicine, 76, 14-20. .
Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P. & Soubrier, F. (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. The Journal of Clinical Investigation, 86(4), 1343-1346.
Zheng, H., & Cao, J. J. (2020). ACE gene polymorphism and severe lung injury in patients with COVID-19..
Gemmati, D., & Tisato, V. (2020). Genetic hypothesis and pharmacogenetics side of renin-angiotensin-system in COVID-19. Genes, 11(9), 1044..
Akbari, M., Taheri, M., Mehrpoor, G., Eslami, S., Hussen, B. M., Ghafouri-Fard, S. & Arefian, N. (2022). Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients. Vascular Pharmacology, 142, 106934..
Yaeghmaie, R., Ghafouri-Fard, S., Noroozi, R., Tavakoli, F., Taheri, M. & Ayatollahi, S. A. (2018). Polymorphisms in the angiotensin I converting enzyme (ACE) gene are associated with multiple sclerosis risk and response to interferon-β treatment. International Immunopharmacology, 64, 275-279.
Mesrian Tanha, H., Mojtabavi Naeini, M., Rahgozar, S., Rasa, S. M. M., & Vallian, S. (2015). Modified tetra-primer ARMS PCR as a single-nucleotide polymorphism genotyping tool. Genetic testing and molecular biomarkers, 19(3), 156-161.
Rubio, M. A. T., Rinehart, J. J., Krett, B., Duvezin-Caubet, S., Reichert, A. S., Söll, D., & Alfonzo, J. D. (2008). Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import. Proceedings of the National Academy of Sciences, 105(27), 9186-9191.
Graffelman, J., Jain, D., & Weir, B. (2017). A genome-wide study of Hardy–Weinberg equilibrium with next generation sequence data. Human genetics, 136(6), 727-741.
Magrone, T., Magrone, M., & Jirillo, E. (2020). Focus on receptors for coronaviruses with special reference to angiotensin-converting enzyme 2 as a potential drug target-a perspective. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets-Immune, Endocrine & Metabolic Disorders), 20(6), 807-811.
Marshall, R. P., Webb, S., Bellingan, G. J., Montgomery, H. E., Chaudhari, B., McAnulty, R. J., ... & Laurent, G. J. (2002). Angiotensin-converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. American Journal of Respiratory and Critical care medicine, 166(5), 646-650.
Khamlaoui, W., Mehri, S., Hammami, S., Elosua, R. & Hammami, M. (2020). Association of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGT M235T) polymorphisms with the risk of obesity in a Tunisian population. Journal of the Renin-Angiotensin-Aldosterone System, 21(2), 147032032090 7820.
Darbani, B. (2020). The expression and polymorphism of entry machinery for COVID-19 in human: juxtaposing population groups, gender, and different tissues. International Journal of Environmental Research and Public Health, 17(10), 3433.
Chen, J., Wang, R., Wang, M. & Wei, G. W. (2020). Mutations strengthened SARS-CoV-2 infectivity. Journal of Molecular Biology, 432(19), 5212-5226.
Pouladi, N. & Abdolahi, S. (2021). Investigating the ACE2 polymorphisms in COVID‐19 susceptibility: An in silico analysis. Molecular Genetics & Genomic Medicine, 9(6), e1672.
Patel, S. K., Wai, B., Ord, M., MacIsaac, R. J., Grant, S., Velkoska, E., ... & Burrell, L. M. (2012). Association of ACE2 genetic variants with blood pressure, left ventricular mass, and cardiac function in Caucasians with type 2 diabetes. American Journal of Hypertension, 25(2), 216-222.
Wooster, L., Nicholson, C. J., Sigurslid, H. H., Cardenas, C. L. L. & Malhotra, R. (2020). Polymorphisms in the ACE2 locus associate with severity of COVID-19 infection. medRxiv.
Xiao, K., Zhai, J., Feng, Y. et al. (2020). Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature 583, 286–289. https://doi.org/10.1038/s41586-020-2313-x
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