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Published in: Virology Journal 1/2022

Open Access 01-12-2022 | SARS-CoV-2 | Research

SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease

Authors: Nahid Alimoradi, Moein Sharqi, Dena Firouzabadi, Mohammad Moein Sadeghi, Mohammad Iman Moezzi, Negar Firouzabadi

Published in: Virology Journal | Issue 1/2022

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Abstract

COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR–RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4–15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05–6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05–35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4–12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73–4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2–3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7–10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4–9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants.
Literature
1.
go back to reference Yang, W., et al. (2020) The role of imaging in 2019 novel coronavirus pneumonia (COVID-19). European radiology 30: 1-9. Yang, W., et al. (2020) The role of imaging in 2019 novel coronavirus pneumonia (COVID-19). European radiology 30: 1-9.
4.
go back to reference Shang, J., et al., Structure of 2019-nCoV chimeric receptor-binding domain complexed with its receptor human ACE2. Worldw. Protein Data Bank (2020). Shang, J., et al., Structure of 2019-nCoV chimeric receptor-binding domain complexed with its receptor human ACE2. Worldw. Protein Data Bank (2020).
6.
go back to reference Li F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol. 2015;89(4):1954–64.PubMedCrossRef Li F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol. 2015;89(4):1954–64.PubMedCrossRef
8.
go back to reference Bahramali E, et al. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case–control study. BMJ Open. 2016;6(2):e010282.PubMedPubMedCentralCrossRef Bahramali E, et al. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case–control study. BMJ Open. 2016;6(2):e010282.PubMedPubMedCentralCrossRef
9.
go back to reference Sekuri C, et al. Renin-angiotensin system gene polymorphisms and premature coronary heart disease. J Renin Angiotensin Aldosterone Syst. 2005;6(1):38–42.PubMedCrossRef Sekuri C, et al. Renin-angiotensin system gene polymorphisms and premature coronary heart disease. J Renin Angiotensin Aldosterone Syst. 2005;6(1):38–42.PubMedCrossRef
10.
11.
go back to reference Vaduganathan M, et al. Renin–angiotensin–aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382(17):1653–9.PubMedCrossRef Vaduganathan M, et al. Renin–angiotensin–aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382(17):1653–9.PubMedCrossRef
12.
go back to reference Ferrario CM. The renin-angiotensin system: importance in physiology and pathology. J Cardiovasc Pharmacol. 1990;15:S1-5.PubMedCrossRef Ferrario CM. The renin-angiotensin system: importance in physiology and pathology. J Cardiovasc Pharmacol. 1990;15:S1-5.PubMedCrossRef
13.
go back to reference Li X, et al. Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis. Heart. 2020;106(15):1142–7.PubMedCrossRef Li X, et al. Impact of cardiovascular disease and cardiac injury on in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis. Heart. 2020;106(15):1142–7.PubMedCrossRef
14.
go back to reference Sabatino J, et al. Impact of cardiovascular risk profile on COVID-19 outcome. A meta-analysis. PLoS ONE. 2020;15(8):1023.CrossRef Sabatino J, et al. Impact of cardiovascular risk profile on COVID-19 outcome. A meta-analysis. PLoS ONE. 2020;15(8):1023.CrossRef
15.
go back to reference Shamshirian, A., et al., Cardiovascular diseases and COVID-19 mortality and intensive care unit admission: A systematic review and meta-analysis. medRxiv, 2020. Shamshirian, A., et al., Cardiovascular diseases and COVID-19 mortality and intensive care unit admission: A systematic review and meta-analysis. medRxiv, 2020.
16.
go back to reference Shenoy V, et al. The angiotensin-converting enzyme 2/angiogenesis-(1–7)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med. 2010;182(8):1065–72.PubMedPubMedCentralCrossRef Shenoy V, et al. The angiotensin-converting enzyme 2/angiogenesis-(1–7)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med. 2010;182(8):1065–72.PubMedPubMedCentralCrossRef
17.
go back to reference Wösten-van Asperen RM, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1–7) or an angiotensin II receptor antagonist. J Pathol. 2011;225(4):618–27.PubMedCrossRef Wösten-van Asperen RM, et al. Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1–7) or an angiotensin II receptor antagonist. J Pathol. 2011;225(4):618–27.PubMedCrossRef
18.
go back to reference Yan F, et al. Antihypertensive drugs are associated with reduced fatal outcomes and improved clinical characteristics in elderly COVID-19 patients. Cell Discov. 2020;6(1):1–10.CrossRef Yan F, et al. Antihypertensive drugs are associated with reduced fatal outcomes and improved clinical characteristics in elderly COVID-19 patients. Cell Discov. 2020;6(1):1–10.CrossRef
19.
go back to reference Yang, G., et al., Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors usage is associated with improved inflammatory status and clinical outcomes in COVID-19 patients with hypertension. MedRxiv, 2020. Yang, G., et al., Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors usage is associated with improved inflammatory status and clinical outcomes in COVID-19 patients with hypertension. MedRxiv, 2020.
20.
go back to reference Sun, M., et al., Inhibitors of RAS might be a good choice for the therapy of COVID-19 pneumonia. Zhonghua jie he he hu xi za zhi= Zhonghua jiehe he huxi zazhi= Chinese journal of tuberculosis and respiratory diseases, 2020. 43:E014-E014. Sun, M., et al., Inhibitors of RAS might be a good choice for the therapy of COVID-19 pneumonia. Zhonghua jie he he hu xi za zhi= Zhonghua jiehe he huxi zazhi= Chinese journal of tuberculosis and respiratory diseases, 2020. 43:E014-E014.
21.
go back to reference Wu J, et al. Advances in research on ACE2 as a receptor for 2019-nCoV. Cell Mol Life Sci. 2021;78(2):531–44.PubMedCrossRef Wu J, et al. Advances in research on ACE2 as a receptor for 2019-nCoV. Cell Mol Life Sci. 2021;78(2):531–44.PubMedCrossRef
22.
go back to reference Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5(4):562–9.PubMedCrossRef Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5(4):562–9.PubMedCrossRef
23.
go back to reference Costa LB, et al. Insights on SARS-CoV-2 molecular interactions with the renin-angiotensin system. Front Cell Dev Biol. 2020;8:55.CrossRef Costa LB, et al. Insights on SARS-CoV-2 molecular interactions with the renin-angiotensin system. Front Cell Dev Biol. 2020;8:55.CrossRef
24.
go back to reference Hamming I, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol J Pathol Soc Great Britain Ireland. 2004;203(2):631–7. Hamming I, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol J Pathol Soc Great Britain Ireland. 2004;203(2):631–7.
25.
go back to reference Donoghue M, et al. A novel angiotensin-converting enzyme–related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2000;87(5):e1–9.PubMedCrossRef Donoghue M, et al. A novel angiotensin-converting enzyme–related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 2000;87(5):e1–9.PubMedCrossRef
26.
go back to reference Vickers C, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277(17):14838–43.PubMedCrossRef Vickers C, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277(17):14838–43.PubMedCrossRef
27.
go back to reference Chappel M, Ferrario C. ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin-(1–7). Kidney Int. 2006;70(1):8–10.PubMedCrossRef Chappel M, Ferrario C. ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin-(1–7). Kidney Int. 2006;70(1):8–10.PubMedCrossRef
28.
go back to reference Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020;46(6):1105–8.PubMedPubMedCentralCrossRef Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020;46(6):1105–8.PubMedPubMedCentralCrossRef
29.
go back to reference Liu Z, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020;92(6):595–601.PubMedCrossRef Liu Z, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020;92(6):595–601.PubMedCrossRef
30.
go back to reference Liu Y, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364–74.PubMedPubMedCentralCrossRef Liu Y, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364–74.PubMedPubMedCentralCrossRef
31.
go back to reference Nukiwa T, et al. Responses of serum and lung angiotensin-converting enzyme activities in the early phase of pulmonary damage induced by oleic acid in dogs. Am Rev Respir Dis. 1982;126(6):1080–6.PubMed Nukiwa T, et al. Responses of serum and lung angiotensin-converting enzyme activities in the early phase of pulmonary damage induced by oleic acid in dogs. Am Rev Respir Dis. 1982;126(6):1080–6.PubMed
32.
go back to reference Dandona P, et al. Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens. 2007;21(1):20–7.PubMedCrossRef Dandona P, et al. Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens. 2007;21(1):20–7.PubMedCrossRef
33.
34.
35.
go back to reference Chaoxin J, et al. 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.PubMed Chaoxin J, et al. 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.PubMed
36.
go back to reference Gemmati D, Tisato V. Genetic hypothesis and pharmacogenetics side of renin-angiotensin-system in COVID-19. Genes. 2020;11(9):1044.PubMedCentralCrossRef Gemmati D, Tisato V. Genetic hypothesis and pharmacogenetics side of renin-angiotensin-system in COVID-19. Genes. 2020;11(9):1044.PubMedCentralCrossRef
37.
go back to reference Alimoradi N, Firouzabadi N. impact of genetics on predisposition and prognosis of COVID-19. Trends Pharmaceut Sci. 2021;7(2):10. Alimoradi N, Firouzabadi N. impact of genetics on predisposition and prognosis of COVID-19. Trends Pharmaceut Sci. 2021;7(2):10.
38.
go back to reference Barash A, et al. The pursuit of COVID-19 biomarkers: putting the spotlight on ACE2 and TMPRSS2 regulatory sequences. Front Med. 2020;7:10.CrossRef Barash A, et al. The pursuit of COVID-19 biomarkers: putting the spotlight on ACE2 and TMPRSS2 regulatory sequences. Front Med. 2020;7:10.CrossRef
39.
go back to reference Srivastava A, et al. Genetic association of ACE2 rs2285666 polymorphism with COVID-19 spatial distribution in India. Front Genet. 2020;11:1163.CrossRef Srivastava A, et al. Genetic association of ACE2 rs2285666 polymorphism with COVID-19 spatial distribution in India. Front Genet. 2020;11:1163.CrossRef
40.
go back to reference Çelik, S.K., et al., Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19; a case study. J Med Virol 2021. Çelik, S.K., et al., Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19; a case study. J Med Virol 2021.
41.
go back to reference Patel SK, et al. From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension. Front Physiol. 2014;5:227.PubMedPubMedCentralCrossRef Patel SK, et al. From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension. Front Physiol. 2014;5:227.PubMedPubMedCentralCrossRef
42.
go back to reference Calcagnile M, et al. Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 Spike protein. Biochimie. 2021;180:143–8.PubMedCrossRef Calcagnile M, et al. Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 Spike protein. Biochimie. 2021;180:143–8.PubMedCrossRef
43.
go back to reference Ashoor, D., et al., A computational approach to evaluate the combined effect of SARS-CoV-2 RBD mutations and ACE2 receptor genetic variants on infectivity: The COVID-19 host-pathogen nexus. bioRxiv, 2021: p. 2020.10. 23.352344. Ashoor, D., et al., A computational approach to evaluate the combined effect of SARS-CoV-2 RBD mutations and ACE2 receptor genetic variants on infectivity: The COVID-19 host-pathogen nexus. bioRxiv, 2021: p. 2020.10. 23.352344.
44.
go back to reference Pouladi N, Abdolahi S. Investigating the ACE2 polymorphisms in COVID-19 susceptibility: an in silico analysis. Mol Genet Genomic Med. 2021;10:e1672. Pouladi N, Abdolahi S. Investigating the ACE2 polymorphisms in COVID-19 susceptibility: an in silico analysis. Mol Genet Genomic Med. 2021;10:e1672.
45.
go back to reference Firouzabadi N, et al. Interaction of A-240T and A2350G related genotypes of angiotensin-converting enzyme (ACE) is associated with decreased serum ACE activity and blood pressure in a healthy Iranian population. Eur J Pharmacol. 2011;668(1–2):241–7.PubMedCrossRef Firouzabadi N, et al. Interaction of A-240T and A2350G related genotypes of angiotensin-converting enzyme (ACE) is associated with decreased serum ACE activity and blood pressure in a healthy Iranian population. Eur J Pharmacol. 2011;668(1–2):241–7.PubMedCrossRef
46.
go back to reference Firouzabadi N, et al. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population. Psychiatry Res. 2012;200(2–3):336–42.PubMedCrossRef Firouzabadi N, et al. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population. Psychiatry Res. 2012;200(2–3):336–42.PubMedCrossRef
47.
go back to reference Zhu X, et al. Linkage and association analysis of angiotensin I–converting enzyme (ACE)–gene polymorphisms with ACE concentration and blood pressure. Am J Human Genet. 2001;68(5):1139–48.CrossRef Zhu X, et al. Linkage and association analysis of angiotensin I–converting enzyme (ACE)–gene polymorphisms with ACE concentration and blood pressure. Am J Human Genet. 2001;68(5):1139–48.CrossRef
49.
go back to reference Leger T, et al. Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score. PLoS ONE. 2020;15(11):e0241407.PubMedPubMedCentralCrossRef Leger T, et al. Low-dose chest CT for diagnosing and assessing the extent of lung involvement of SARS-CoV-2 pneumonia using a semi quantitative score. PLoS ONE. 2020;15(11):e0241407.PubMedPubMedCentralCrossRef
50.
go back to reference MWer S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.CrossRef MWer S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.CrossRef
51.
go back to reference Zhong J, et al. Association of angiotensin-converting enzyme 2 gene A/G polymorphism and elevated blood pressure in Chinese patients with metabolic syndrome. J Lab Clin Med. 2006;147(2):91–5.PubMedPubMedCentralCrossRef Zhong J, et al. Association of angiotensin-converting enzyme 2 gene A/G polymorphism and elevated blood pressure in Chinese patients with metabolic syndrome. J Lab Clin Med. 2006;147(2):91–5.PubMedPubMedCentralCrossRef
52.
go back to reference Iqbal MP, et al. Association study of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with myocardial infarction. Exp Mol Med. 2004;36(2):110–5.PubMedCrossRef Iqbal MP, et al. Association study of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with myocardial infarction. Exp Mol Med. 2004;36(2):110–5.PubMedCrossRef
53.
go back to reference Firouzabadi N, et al. Impact of ACE 2 genetic variant on antidepressant efficacy of SSRIs. Acta Neuropsychiatrica. 2021;10:1–25. Firouzabadi N, et al. Impact of ACE 2 genetic variant on antidepressant efficacy of SSRIs. Acta Neuropsychiatrica. 2021;10:1–25.
54.
go back to reference Firouzabadi N, et al. Gender specificity of a genetic variant of angiotensin-converting enzyme and risk of coronary artery disease. Mol Biol Rep. 2013;40(8):4959–65.PubMedCrossRef Firouzabadi N, et al. Gender specificity of a genetic variant of angiotensin-converting enzyme and risk of coronary artery disease. Mol Biol Rep. 2013;40(8):4959–65.PubMedCrossRef
55.
56.
go back to reference Wang, Q., et al., Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 2020;181(4):894–904. e9. Wang, Q., et al., Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 2020;181(4):894–904. e9.
57.
go back to reference Santos RAS, et al. The ACE2/angiotensin-(1–7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7). Physiol Rev. 2017;98:505–53.PubMedCentralCrossRef Santos RAS, et al. The ACE2/angiotensin-(1–7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7). Physiol Rev. 2017;98:505–53.PubMedCentralCrossRef
58.
go back to reference Xu H, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):1–5.CrossRef Xu H, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):1–5.CrossRef
59.
go back to reference Rice GI, et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383(1):45–51.PubMedPubMedCentralCrossRef Rice GI, et al. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochem J. 2004;383(1):45–51.PubMedPubMedCentralCrossRef
60.
go back to reference Li Y, et al. Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways. Sci Rep. 2016;6(1):1–14. Li Y, et al. Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways. Sci Rep. 2016;6(1):1–14.
61.
go back to reference Magalhaes GS, et al. Angiotensin-(1–7) promotes resolution of eosinophilic inflammation in an experimental model of asthma. Front Immunol. 2018;9:58.PubMedPubMedCentralCrossRef Magalhaes GS, et al. Angiotensin-(1–7) promotes resolution of eosinophilic inflammation in an experimental model of asthma. Front Immunol. 2018;9:58.PubMedPubMedCentralCrossRef
62.
go back to reference Wang D, et al. Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation. Pulmonary Pharmacol Therapeut. 2019;58:101.CrossRef Wang D, et al. Renin-angiotensin-system, a potential pharmacological candidate, in acute respiratory distress syndrome during mechanical ventilation. Pulmonary Pharmacol Therapeut. 2019;58:101.CrossRef
63.
go back to reference He H, et al. Mesenchymal stem cells overexpressing angiotensin-converting enzyme 2 rescue lipopolysaccharide-induced lung injury. Cell Transplant. 2015;24(9):1699–715.PubMedCrossRef He H, et al. Mesenchymal stem cells overexpressing angiotensin-converting enzyme 2 rescue lipopolysaccharide-induced lung injury. Cell Transplant. 2015;24(9):1699–715.PubMedCrossRef
64.
go back to reference Bastos AC, et al. Oral formulation angiotensin-(1–7) therapy attenuates pulmonary and systemic damage in mice with emphysema induced by elastase. Immunobiology. 2020;225(2):151893.PubMedCrossRef Bastos AC, et al. Oral formulation angiotensin-(1–7) therapy attenuates pulmonary and systemic damage in mice with emphysema induced by elastase. Immunobiology. 2020;225(2):151893.PubMedCrossRef
66.
go back to reference Magalhaes GS, et al. Activation of Ang-(1–7)/Mas receptor is a possible strategy to treat coronavirus (SARS-CoV-2) infection. Front Physiol. 2020;11:730.PubMedPubMedCentralCrossRef Magalhaes GS, et al. Activation of Ang-(1–7)/Mas receptor is a possible strategy to treat coronavirus (SARS-CoV-2) infection. Front Physiol. 2020;11:730.PubMedPubMedCentralCrossRef
67.
go back to reference Chappell MC, Al Zayadneh EM. Angiotensin-(1–7) and the regulation of anti-fibrotic signaling pathways. J Cell Signal. 2017;2(1):10.CrossRef Chappell MC, Al Zayadneh EM. Angiotensin-(1–7) and the regulation of anti-fibrotic signaling pathways. J Cell Signal. 2017;2(1):10.CrossRef
68.
go back to reference Gironacci MM. Angiotensin-(1–7): beyond its central effects on blood pressure. Ther Adv Cardiovasc Dis. 2015;9(4):209–16.PubMedCrossRef Gironacci MM. Angiotensin-(1–7): beyond its central effects on blood pressure. Ther Adv Cardiovasc Dis. 2015;9(4):209–16.PubMedCrossRef
69.
70.
go back to reference Wu YH, et al. The ACE 2 G8790A polymorphism: involvement in type 2 diabetes mellitus combined with cerebral stroke. J Clin Lab Anal. 2017;31(2):e22033.CrossRef Wu YH, et al. The ACE 2 G8790A polymorphism: involvement in type 2 diabetes mellitus combined with cerebral stroke. J Clin Lab Anal. 2017;31(2):e22033.CrossRef
71.
go back to reference Wang Z, et al. Immune responses with DNA vaccines encoded different gene fragments of severe acute respiratory syndrome coronavirus in BALB/c mice. Biochem Biophys Res Commun. 2005;327(1):130–5.PubMedCrossRef Wang Z, et al. Immune responses with DNA vaccines encoded different gene fragments of severe acute respiratory syndrome coronavirus in BALB/c mice. Biochem Biophys Res Commun. 2005;327(1):130–5.PubMedCrossRef
72.
go back to reference Möhlendick B, et al. ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19. Pharmacogenet Genom. 2021;31:165–71.CrossRef Möhlendick B, et al. ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19. Pharmacogenet Genom. 2021;31:165–71.CrossRef
73.
go back to reference Karakaş Çelik S, et al. Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: a case study. J Med Virol. 2021;93(10):5947–52.PubMedPubMedCentralCrossRef Karakaş Çelik S, et al. Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: a case study. J Med Virol. 2021;93(10):5947–52.PubMedPubMedCentralCrossRef
78.
go back to reference Hoffmann, M., 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):271–280.e8. Hoffmann, M., 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):271–280.e8.
79.
go back to reference Walls, A.C., et al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020;181(2): 281–292.e6. Walls, A.C., et al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020;181(2): 281–292.e6.
80.
go back to reference Mahmood MS, et al. Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension. J Hum Hypertens. 2003;17(10):719–23.CrossRef Mahmood MS, et al. Association of the angiotensin-converting enzyme (ACE) gene G2350A dimorphism with essential hypertension. J Hum Hypertens. 2003;17(10):719–23.CrossRef
81.
go back to reference Schüler R, et al. High-saturated-fat diet increases circulating angiotensin-converting enzyme, which is enhanced by the rs4343 polymorphism defining persons at risk of nutrient-dependent increases of blood pressure. J Am Heart Assoc. 2017;6(1):e004465.PubMedPubMedCentralCrossRef Schüler R, et al. High-saturated-fat diet increases circulating angiotensin-converting enzyme, which is enhanced by the rs4343 polymorphism defining persons at risk of nutrient-dependent increases of blood pressure. J Am Heart Assoc. 2017;6(1):e004465.PubMedPubMedCentralCrossRef
82.
go back to reference Watanabe T, Barker TA, Berk BC. Angiotensin II and the endothelium: diverse signals and effects. Hypertension. 2005;45(2):163–9.PubMedCrossRef Watanabe T, Barker TA, Berk BC. Angiotensin II and the endothelium: diverse signals and effects. Hypertension. 2005;45(2):163–9.PubMedCrossRef
83.
go back to reference Senchenkova EY, et al. Angiotensin II–mediated microvascular thrombosis. Hypertension. 2010;56(6):1089–95.PubMedCrossRef Senchenkova EY, et al. Angiotensin II–mediated microvascular thrombosis. Hypertension. 2010;56(6):1089–95.PubMedCrossRef
84.
go back to reference Tay K-H, Lip GY. What “drives” the link between the renin–angiotensin–aldosterone system and the prothrombotic state in hypertension? Oxford: Oxford University Press; 2008.CrossRef Tay K-H, Lip GY. What “drives” the link between the renin–angiotensin–aldosterone system and the prothrombotic state in hypertension? Oxford: Oxford University Press; 2008.CrossRef
86.
go back to reference Biswas S, et al. Blood clots in COVID-19 patients: simplifying the curious mystery. Med Hypotheses. 2021;146:110371.PubMedCrossRef Biswas S, et al. Blood clots in COVID-19 patients: simplifying the curious mystery. Med Hypotheses. 2021;146:110371.PubMedCrossRef
87.
go back to reference Ferreira AJ, et al. New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1–7)/mas receptor axis. Int J Hypertens. 2012;2012:5. Ferreira AJ, et al. New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1–7)/mas receptor axis. Int J Hypertens. 2012;2012:5.
88.
go back to reference Tan WSD, et al. Targeting the renin–angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr Opin Pharmacol. 2018;40:9–17.PubMedCrossRef Tan WSD, et al. Targeting the renin–angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr Opin Pharmacol. 2018;40:9–17.PubMedCrossRef
89.
go back to reference Srivastava P, et al. Imbalance between Angiotensin II-Angiotensin (1–7) system is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension. Diabetes Metab Syndr. 2019;13(3):2061–8.PubMedCrossRef Srivastava P, et al. Imbalance between Angiotensin II-Angiotensin (1–7) system is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension. Diabetes Metab Syndr. 2019;13(3):2061–8.PubMedCrossRef
90.
go back to reference Cook JR, Ausiello J. Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19. Rev Endocrine Metabolic Disord. 2021;10:1–20. Cook JR, Ausiello J. Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19. Rev Endocrine Metabolic Disord. 2021;10:1–20.
91.
go back to reference Lanza K, et al. Covid-19: the renin–angiotensin system imbalance hypothesis. Clin Sci. 2020;134(11):1259–64.CrossRef Lanza K, et al. Covid-19: the renin–angiotensin system imbalance hypothesis. Clin Sci. 2020;134(11):1259–64.CrossRef
92.
go back to reference Killerby ME, et al. Characteristics associated with hospitalization among patients with COVID-19—Metropolitan Atlanta, Georgia, March–April 2020. Morb Mortal Wkly Rep. 2020;69(25):790.CrossRef Killerby ME, et al. Characteristics associated with hospitalization among patients with COVID-19—Metropolitan Atlanta, Georgia, March–April 2020. Morb Mortal Wkly Rep. 2020;69(25):790.CrossRef
Metadata
Title
SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease
Authors
Nahid Alimoradi
Moein Sharqi
Dena Firouzabadi
Mohammad Moein Sadeghi
Mohammad Iman Moezzi
Negar Firouzabadi
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2022
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-022-01782-6

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