Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 8/2021

01-08-2021 | Severe Acute Respiratory Syndrome Coronavirus | Review

Epigenetic alterations and genetic variations of angiotensin-converting enzyme 2 (ACE2) as a functional receptor for SARS-CoV-2: potential clinical implications

Authors: Anvarsadat Kianmehr, Isabella Faraoni, Omer Kucuk, Abdolkarim Mahrooz

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 8/2021

Login to get access

Abstract

Receptor recognition is a crucial step in viral infection and is a critical factor for cell entry and tissue tropism. In several recent studies, angiotensin-converting enzyme 2 (ACE2) has been demonstrated to be the cellular receptor of SARS-CoV-2 as it was previously well known as the receptor of SARS-CoV. SARS-CoV-2 can bind with high affinity to human ACE2 and engages it as an entry receptor. It seems that the genetic, notably epigenetic variations of ACE2 are less known in different populations, indicating the need for its further investigation. These variations have the potential to affect its contribution to the pathogenicity of COVID-19. The contribution of epigenetics in the interindividual variability of ACE2 merits more attention because epigenetic processes can play important roles in ACE2 alterations in various tissues and different people and populations. Analyzing different DNA methylation patterns and microRNAs, contributing to the ACE2 modulation in the lungs will have a high priority. The epigenetic and genetic variations of ACE2 become even more important when considering that some people have mild clinical symptoms despite having COVID-19. The pathogenicity of SARS-CoV-2 infection is complex; therefore, a better understanding of the underlying pathobiology, especially binding the virus to its receptors, could help improve therapeutic and preventive approaches. This review aims to highlight the importance of evaluating both the epigenetic and genetic variations of ACE2 as a receptor for the deadly SARS-CoV-2.
Literature
1.
go back to reference Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (2020) Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A Review. JAMA. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (2020) Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A Review. JAMA.
2.
go back to reference Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell.
3.
go back to reference Sodhi CP, Wohlford-Lenane C, Yamaguchi Y, Prindle T, Fulton WB, Wang S et al (2018) Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. Am J Phys Lung Cell Mol Phys 314(1):L17–L31 Sodhi CP, Wohlford-Lenane C, Yamaguchi Y, Prindle T, Fulton WB, Wang S et al (2018) Attenuation of pulmonary ACE2 activity impairs inactivation of des-Arg9 bradykinin/BKB1R axis and facilitates LPS-induced neutrophil infiltration. Am J Phys Lung Cell Mol Phys 314(1):L17–L31
4.
go back to reference Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD et al (2007) The emerging role of ACE2 in physiology and disease. J Pathol 212(1):1–11PubMedPubMedCentralCrossRef Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD et al (2007) The emerging role of ACE2 in physiology and disease. J Pathol 212(1):1–11PubMedPubMedCentralCrossRef
5.
go back to reference Burrell LM, Harrap SB, Velkoska E, Patel SK (2013) The ACE2 gene: its potential as a functional candidate for cardiovascular disease. Clin Sci 124(2):65–76CrossRef Burrell LM, Harrap SB, Velkoska E, Patel SK (2013) The ACE2 gene: its potential as a functional candidate for cardiovascular disease. Clin Sci 124(2):65–76CrossRef
6.
go back to reference Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) 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:1–8 Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020) 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:1–8
7.
go back to reference Qi F, Qian S, Zhang S, Zhang Z (2020) Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun Qi F, Qian S, Zhang S, Zhang Z (2020) Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun
8.
go back to reference Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223):497–506PubMedPubMedCentralCrossRef Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223):497–506PubMedPubMedCentralCrossRef
9.
go back to reference Tuttolomondo D, Frizzelli A, Aiello M, Bertorelli G, Majori M, Chetta A (2020) Beyond the lung involvement in COVID-19 patients. A review. Minerva Med Tuttolomondo D, Frizzelli A, Aiello M, Bertorelli G, Majori M, Chetta A (2020) Beyond the lung involvement in COVID-19 patients. A review. Minerva Med
10.
go back to reference Lu R, Zhao X, Li J, Niu P, Yang B, Wu H et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395(10224):565–574PubMedPubMedCentralCrossRef Lu R, Zhao X, Li J, Niu P, Yang B, Wu H et al (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395(10224):565–574PubMedPubMedCentralCrossRef
11.
go back to reference Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q (2020) Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q (2020) Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science.
12.
go back to reference Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Philip N et al (2006) Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest 116(8):2218–2225PubMedPubMedCentralCrossRef Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Philip N et al (2006) Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest 116(8):2218–2225PubMedPubMedCentralCrossRef
13.
go back to reference Yamamoto K, Ohishi M, Katsuya T, Ito N, Ikushima M, Kaibe M et al (2006) Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II. Hypertension. 47(4):718–726PubMedCrossRef Yamamoto K, Ohishi M, Katsuya T, Ito N, Ikushima M, Kaibe M et al (2006) Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II. Hypertension. 47(4):718–726PubMedCrossRef
14.
go back to reference Brosnihan KB, Neves LA, Chappell MC (2005) Does the angiotensin-converting enzyme (ACE)/ACE2 balance contribute to the fate of angiotensin peptides in programmed hypertension? Am Heart Assoc Brosnihan KB, Neves LA, Chappell MC (2005) Does the angiotensin-converting enzyme (ACE)/ACE2 balance contribute to the fate of angiotensin peptides in programmed hypertension? Am Heart Assoc
15.
go back to reference Wakahara S, Konoshita T, Mizuno S, Motomura M, Aoyama C, Makino Y et al (2007) Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 ratio. Endocrinology. 148(5):2453–2457PubMedCrossRef Wakahara S, Konoshita T, Mizuno S, Motomura M, Aoyama C, Makino Y et al (2007) Synergistic expression of angiotensin-converting enzyme (ACE) and ACE2 in human renal tissue and confounding effects of hypertension on the ACE to ACE2 ratio. Endocrinology. 148(5):2453–2457PubMedCrossRef
16.
go back to reference Scialo F, Daniele A, Amato F, Pastore L, Matera MG, Cazzola M et al (2020) ACE2: the major cell entry receptor for SARS-CoV-2. Lung.:1–11 Scialo F, Daniele A, Amato F, Pastore L, Matera MG, Cazzola M et al (2020) ACE2: the major cell entry receptor for SARS-CoV-2. Lung.:1–11
17.
go back to reference Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J et al (2005) ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 79(23):14614–14621PubMedPubMedCentralCrossRef Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J et al (2005) ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 79(23):14614–14621PubMedPubMedCentralCrossRef
18.
go back to reference Sun J, He W-T, Wang L, Lai A, Ji X, Zhai X et al (2020) COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends Mol Med Sun J, He W-T, Wang L, Lai A, Ji X, Zhai X et al (2020) COVID-19: epidemiology, evolution, and cross-disciplinary perspectives. Trends Mol Med
19.
go back to reference Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B et al (2005) Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 436(7047):112–116PubMedPubMedCentralCrossRef Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B et al (2005) Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 436(7047):112–116PubMedPubMedCentralCrossRef
20.
go back to reference Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T et al (2008) Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. Proc Natl Acad Sci 105(22):7809–7814PubMedPubMedCentralCrossRef Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T et al (2008) Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. Proc Natl Acad Sci 105(22):7809–7814PubMedPubMedCentralCrossRef
21.
go back to reference Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S et al (2005) Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J 24(8):1634–1643PubMedPubMedCentralCrossRef Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S et al (2005) Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J 24(8):1634–1643PubMedPubMedCentralCrossRef
22.
go back to reference Mahrooz A, Muscogiuri G, Buzzetti R, Maddaloni E (2021) The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism. Endocrine. 2021/04/22 Mahrooz A, Muscogiuri G, Buzzetti R, Maddaloni E (2021) The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism. Endocrine. 2021/04/22
23.
go back to reference Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 94(7) Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 94(7)
24.
go back to reference McCray PB, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L et al (2007) Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol 81(2):813–821PubMedCrossRef McCray PB, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L et al (2007) Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol 81(2):813–821PubMedCrossRef
25.
go back to reference Yang X-L, Hu B, Wang B, Wang M-N, Zhang Q, Zhang W et al (2016) Isolation and characterization of a novel bat coronavirus closely related to the direct progenitor of severe acute respiratory syndrome coronavirus. J Virol 90(6):3253–3256PubMedCentralCrossRef Yang X-L, Hu B, Wang B, Wang M-N, Zhang Q, Zhang W et al (2016) Isolation and characterization of a novel bat coronavirus closely related to the direct progenitor of severe acute respiratory syndrome coronavirus. J Virol 90(6):3253–3256PubMedCentralCrossRef
26.
go back to reference Hou Y, Peng C, Yu M, Li Y, Han Z, Li F et al (2010) Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry. Arch Virol 155(10):1563–1569PubMedPubMedCentralCrossRef Hou Y, Peng C, Yu M, Li Y, Han Z, Li F et al (2010) Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry. Arch Virol 155(10):1563–1569PubMedPubMedCentralCrossRef
27.
go back to reference Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 367(6483):1260–1263PubMedPubMedCentralCrossRef Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh C-L, Abiona O et al (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 367(6483):1260–1263PubMedPubMedCentralCrossRef
28.
go back to reference Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H et al (2020) Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H et al (2020) Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol
29.
go back to reference Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell.
30.
go back to reference Mirmohammadi S, Kianmehr A, Arefi M, Mahrooz A (2020) Biochemical parameters and pathogenesis of SARS-CoV-2 infection in vital organs: COVID-19 outbreak in Iran. New Microbes New Infect 100792 Mirmohammadi S, Kianmehr A, Arefi M, Mahrooz A (2020) Biochemical parameters and pathogenesis of SARS-CoV-2 infection in vital organs: COVID-19 outbreak in Iran. New Microbes New Infect 100792
31.
go back to reference Fan Z, Wu G, Yue M, Ye J, Chen Y, Xu B et al (2019) Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism. Life Sci 225:39–45PubMedCrossRef Fan Z, Wu G, Yue M, Ye J, Chen Y, Xu B et al (2019) Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism. Life Sci 225:39–45PubMedCrossRef
32.
go back to reference Bunyavanich S, Grant C, Vicencio A (2020) Racial/ethnic variation in nasal gene expression of transmembrane serine protease 2 (TMPRSS2). Jama. 324(15):1567–1568PubMedCrossRef Bunyavanich S, Grant C, Vicencio A (2020) Racial/ethnic variation in nasal gene expression of transmembrane serine protease 2 (TMPRSS2). Jama. 324(15):1567–1568PubMedCrossRef
33.
go back to reference Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T et al (2004) ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem 279(17):17996–18007PubMedCrossRef Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T et al (2004) ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem 279(17):17996–18007PubMedCrossRef
34.
go back to reference Jia H (2016) Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease. Shock. 46(3):239–248PubMedCrossRef Jia H (2016) Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease. Shock. 46(3):239–248PubMedCrossRef
35.
go back to reference Kuba K, Imai Y, Penninger JM (2013) Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J 77(2):301–308PubMedCrossRef Kuba K, Imai Y, Penninger JM (2013) Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J 77(2):301–308PubMedCrossRef
36.
go back to reference Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS (2020) Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med:1–5 Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS (2020) Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med:1–5
37.
go back to reference Qiu Y, Zhao Y-B, Wang Q, Li J-Y, Zhou Z-J, Liao C-H et al (2020) Predicting the angiotensin converting enzyme 2 (ACE2) utilizing capability as the receptor of SARS-CoV-2. Microbes Infect Qiu Y, Zhao Y-B, Wang Q, Li J-Y, Zhou Z-J, Liao C-H et al (2020) Predicting the angiotensin converting enzyme 2 (ACE2) utilizing capability as the receptor of SARS-CoV-2. Microbes Infect
38.
go back to reference Li R, Qiao S, Zhang G (2020) Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV. J Infect Li R, Qiao S, Zhang G (2020) Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCoV. J Infect
39.
go back to reference Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W et al (2020) Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182(4):812–27.e19PubMedPubMedCentralCrossRef Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W et al (2020) Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182(4):812–27.e19PubMedPubMedCentralCrossRef
40.
go back to reference Daugherty MD, Malik HS (2012) Rules of engagement: molecular insights from host-virus arms races. Annu Rev Genet 46:677–700PubMedCrossRef Daugherty MD, Malik HS (2012) Rules of engagement: molecular insights from host-virus arms races. Annu Rev Genet 46:677–700PubMedCrossRef
41.
go back to reference Rice GI, Jones AL, Grant PJ, Carter AM, Turner AJ, Hooper NM (2006) Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study. Hypertension. 48(5):914–920PubMedCrossRef Rice GI, Jones AL, Grant PJ, Carter AM, Turner AJ, Hooper NM (2006) Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study. Hypertension. 48(5):914–920PubMedCrossRef
42.
go back to reference Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X et al (2020) Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov 6(1):1–4CrossRef Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X et al (2020) Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov 6(1):1–4CrossRef
43.
go back to reference Kuan T-C, Yang T-H, Wen C-H, Chen M-Y, Lee I-L, Lin C-S (2011) Identifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblasts. Peptides. 32(9):1832–1839PubMedCrossRef Kuan T-C, Yang T-H, Wen C-H, Chen M-Y, Lee I-L, Lin C-S (2011) Identifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblasts. Peptides. 32(9):1832–1839PubMedCrossRef
44.
go back to reference Senkel S, Lucas B, Klein-Hitpass L, Ryffel GU (2005) Identification of target genes of the transcription factor HNF1β and HNF1α in a human embryonic kidney cell line. Biochim Biophys Acta (BBA)-Gene Struct Expr 1731(3):179–190CrossRef Senkel S, Lucas B, Klein-Hitpass L, Ryffel GU (2005) Identification of target genes of the transcription factor HNF1β and HNF1α in a human embryonic kidney cell line. Biochim Biophys Acta (BBA)-Gene Struct Expr 1731(3):179–190CrossRef
45.
go back to reference Pedersen KB, Chhabra KH, Nguyen VK, Xia H, Lazartigues E (2013) The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs. Biochim Biophys Acta (BBA)-Gene Regul Mech 1829(11):1225–1235CrossRef Pedersen KB, Chhabra KH, Nguyen VK, Xia H, Lazartigues E (2013) The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs. Biochim Biophys Acta (BBA)-Gene Regul Mech 1829(11):1225–1235CrossRef
46.
go back to reference Pedersen KB, Chodavarapu H, Lazartigues E (2017) Forkhead box transcription factors of the FOXA class are required for basal transcription of angiotensin-converting enzyme 2. J Endocr Soc 1(4):370–384PubMedPubMedCentralCrossRef Pedersen KB, Chodavarapu H, Lazartigues E (2017) Forkhead box transcription factors of the FOXA class are required for basal transcription of angiotensin-converting enzyme 2. J Endocr Soc 1(4):370–384PubMedPubMedCentralCrossRef
47.
go back to reference Wang Y, Shoemaker R, Thatcher SE, Batifoulier-Yiannikouris F, English VL, Cassis LA (2015) Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism. Am J Physiol-Endocrinol Metab 308(12):E1066–E1E75PubMedPubMedCentralCrossRef Wang Y, Shoemaker R, Thatcher SE, Batifoulier-Yiannikouris F, English VL, Cassis LA (2015) Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism. Am J Physiol-Endocrinol Metab 308(12):E1066–E1E75PubMedPubMedCentralCrossRef
48.
go back to reference Pedersen KB, Chodavarapu H, Porretta C, Robinson LK, Lazartigues E (2015) Dynamics of ADAM17-mediated shedding of ACE2 applied to pancreatic islets of male db/db mice. Endocrinology. 156(12):4411–4425PubMedCrossRef Pedersen KB, Chodavarapu H, Porretta C, Robinson LK, Lazartigues E (2015) Dynamics of ADAM17-mediated shedding of ACE2 applied to pancreatic islets of male db/db mice. Endocrinology. 156(12):4411–4425PubMedCrossRef
49.
go back to reference Malo D, Skamene E (1994) Genetic control of host resistance to infection. Trends Genet 10(10):365–371PubMedCrossRef Malo D, Skamene E (1994) Genetic control of host resistance to infection. Trends Genet 10(10):365–371PubMedCrossRef
50.
go back to reference Itoyama S, Keicho N, Hijikata M, Quy T, Phi NC, Long HT et al (2005) Identification of an alternative 5′-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: Lack of association with SARS in the Vietnamese population. Am J Med Genet A 136(1):52–57PubMedCrossRef Itoyama S, Keicho N, Hijikata M, Quy T, Phi NC, Long HT et al (2005) Identification of an alternative 5′-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: Lack of association with SARS in the Vietnamese population. Am J Med Genet A 136(1):52–57PubMedCrossRef
51.
52.
go back to reference Chiu RW, Tang NL, Hui DS, Chung GT, Chim SS, Chan KA et al (2004) ACE2 gene polymorphisms do not affect outcome of severe acute respiratory syndrome. Clin Chem 50(9):1683–1686PubMedPubMedCentralCrossRef Chiu RW, Tang NL, Hui DS, Chung GT, Chim SS, Chan KA et al (2004) ACE2 gene polymorphisms do not affect outcome of severe acute respiratory syndrome. Clin Chem 50(9):1683–1686PubMedPubMedCentralCrossRef
53.
go back to reference Cavalli G, Heard E (2019) Advances in epigenetics link genetics to the environment and disease. Nature. 571(7766):489–499PubMedCrossRef Cavalli G, Heard E (2019) Advances in epigenetics link genetics to the environment and disease. Nature. 571(7766):489–499PubMedCrossRef
54.
go back to reference Ding N, Maiuri AR, O’Hagan HM (2019) The emerging role of epigenetic modifiers in repair of DNA damage associated with chronic inflammatory diseases. Mutat Res/Rev Mutat Res 780:69–81CrossRef Ding N, Maiuri AR, O’Hagan HM (2019) The emerging role of epigenetic modifiers in repair of DNA damage associated with chronic inflammatory diseases. Mutat Res/Rev Mutat Res 780:69–81CrossRef
55.
go back to reference Mahrooz A, Mackness M, Bagheri A, Ghaffari-Cherati M, Masoumi P (2019) The epigenetic regulation of paraoxonase 1 (PON1) as an important enzyme in HDL function: The missing link between environmental and genetic regulation. Clin Biochem Mahrooz A, Mackness M, Bagheri A, Ghaffari-Cherati M, Masoumi P (2019) The epigenetic regulation of paraoxonase 1 (PON1) as an important enzyme in HDL function: The missing link between environmental and genetic regulation. Clin Biochem
56.
go back to reference Meehan RR, Thomson JP, Lentini A, Nestor CE, Pennings S (2018) DNA methylation as a genomic marker of exposure to chemical and environmental agents. Curr Opin Chem Biol 45:48–56PubMedCrossRef Meehan RR, Thomson JP, Lentini A, Nestor CE, Pennings S (2018) DNA methylation as a genomic marker of exposure to chemical and environmental agents. Curr Opin Chem Biol 45:48–56PubMedCrossRef
57.
go back to reference Mahna D, Puri S, Sharma S (2018) DNA methylation signatures: biomarkers of drug and alcohol abuse. Mutat Res/Rev Mutat Res 777:19–28CrossRef Mahna D, Puri S, Sharma S (2018) DNA methylation signatures: biomarkers of drug and alcohol abuse. Mutat Res/Rev Mutat Res 777:19–28CrossRef
58.
go back to reference Lund G, Zaina S (2009) Atherosclerosis risk factors can impose aberrant DNA methylation patterns: a tale of traffic and homocysteine. Curr Opin Lipidol 20(5):448–449PubMedCrossRef Lund G, Zaina S (2009) Atherosclerosis risk factors can impose aberrant DNA methylation patterns: a tale of traffic and homocysteine. Curr Opin Lipidol 20(5):448–449PubMedCrossRef
59.
go back to reference Xia X (2020) Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol Xia X (2020) Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol
60.
go back to reference Corley MJ, Ndhlovu LC (2020) DNA methylation analysis of the COVID-19 host cell receptor, angiotensin I converting enzyme 2 gene (ACE2) in the respiratory system reveal age and gender differences Corley MJ, Ndhlovu LC (2020) DNA methylation analysis of the COVID-19 host cell receptor, angiotensin I converting enzyme 2 gene (ACE2) in the respiratory system reveal age and gender differences
61.
go back to reference Fan R, Mao SQ, Gu TL, Zhong FD, Gong ML, Hao LM et al (2017) Preliminary analysis of the association between methylation of the ACE2 promoter and essential hypertension. Mol Med Rep 15(6):3905–3911PubMedCrossRef Fan R, Mao SQ, Gu TL, Zhong FD, Gong ML, Hao LM et al (2017) Preliminary analysis of the association between methylation of the ACE2 promoter and essential hypertension. Mol Med Rep 15(6):3905–3911PubMedCrossRef
62.
go back to reference Cardenas A, Rifas-Shiman SL, Sordillo JE, DeMeo DL, Baccarelli AA, Hivert M-F et al (2020) DNA methylation architecture of the ACE2 gene in Nasal Cells. Medrxiv. Cardenas A, Rifas-Shiman SL, Sordillo JE, DeMeo DL, Baccarelli AA, Hivert M-F et al (2020) DNA methylation architecture of the ACE2 gene in Nasal Cells. Medrxiv.
63.
go back to reference Sawalha AH, Zhao M, Coit P, Lu Q (2020) Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clin Immunol 108410 Sawalha AH, Zhao M, Coit P, Lu Q (2020) Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clin Immunol 108410
65.
go back to reference Vaissière T, Sawan C, Herceg Z (2008) Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res/Rev Mutat Res 659(1-2):40–48CrossRef Vaissière T, Sawan C, Herceg Z (2008) Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res/Rev Mutat Res 659(1-2):40–48CrossRef
66.
go back to reference Clarke NE, Belyaev ND, Lambert DW, Turner AJ (2014) Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci 126(7):507–516CrossRef Clarke NE, Belyaev ND, Lambert DW, Turner AJ (2014) Epigenetic regulation of angiotensin-converting enzyme 2 (ACE2) by SIRT1 under conditions of cell energy stress. Clin Sci 126(7):507–516CrossRef
67.
go back to reference Dell’Omo G, Crescenti D, Vantaggiato C, Parravicini C, Borroni AP, Rizzi N et al (2019) Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs. Br J Cancer 120(5):537PubMedPubMedCentralCrossRef Dell’Omo G, Crescenti D, Vantaggiato C, Parravicini C, Borroni AP, Rizzi N et al (2019) Inhibition of SIRT1 deacetylase and p53 activation uncouples the anti-inflammatory and chemopreventive actions of NSAIDs. Br J Cancer 120(5):537PubMedPubMedCentralCrossRef
68.
go back to reference Tikoo K, Patel G, Kumar S, Karpe PA, Sanghavi M, Malek V et al (2015) Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: Role of epigenetic histone modifications. Biochem Pharmacol 93(3):343–351PubMedCrossRef Tikoo K, Patel G, Kumar S, Karpe PA, Sanghavi M, Malek V et al (2015) Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: Role of epigenetic histone modifications. Biochem Pharmacol 93(3):343–351PubMedCrossRef
69.
go back to reference Pinto BG, Oliveira AE, Singh Y, Jimenez L, Goncalves AN, Ogava RL et al (2020) ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. medRxiv Pinto BG, Oliveira AE, Singh Y, Jimenez L, Goncalves AN, Ogava RL et al (2020) ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. medRxiv
70.
go back to reference Pruimboom L (2020) Methylation pathways and SARS-CoV-2 lung infiltration and cell membrane-virus fusion are both subject to epigenetics. Front Cell Infect Microbiol 10:290PubMedPubMedCentralCrossRef Pruimboom L (2020) Methylation pathways and SARS-CoV-2 lung infiltration and cell membrane-virus fusion are both subject to epigenetics. Front Cell Infect Microbiol 10:290PubMedPubMedCentralCrossRef
71.
go back to reference Phillip CJ, Giardina CK, Bilir B, Cutler DJ, Lai Y-H, Kucuk O et al (2012) Genistein cooperates with the histone deacetylase inhibitor vorinostat to induce cell death in prostate cancer cells. BMC Cancer 12(1):145PubMedPubMedCentralCrossRef Phillip CJ, Giardina CK, Bilir B, Cutler DJ, Lai Y-H, Kucuk O et al (2012) Genistein cooperates with the histone deacetylase inhibitor vorinostat to induce cell death in prostate cancer cells. BMC Cancer 12(1):145PubMedPubMedCentralCrossRef
72.
go back to reference Fang Y, Gao F, Hao J, Liu Z (2017) microRNA-1246 mediates lipopolysaccharide-induced pulmonary endothelial cell apoptosis and acute lung injury by targeting angiotensin-converting enzyme 2. Am J Transl Res 9(3):1287PubMedPubMedCentral Fang Y, Gao F, Hao J, Liu Z (2017) microRNA-1246 mediates lipopolysaccharide-induced pulmonary endothelial cell apoptosis and acute lung injury by targeting angiotensin-converting enzyme 2. Am J Transl Res 9(3):1287PubMedPubMedCentral
73.
go back to reference Liu Q, Du J, Yu X, Xu J, Huang F, Li X et al (2017) miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov 3(1):1–17CrossRef Liu Q, Du J, Yu X, Xu J, Huang F, Li X et al (2017) miRNA-200c-3p is crucial in acute respiratory distress syndrome. Cell Discov 3(1):1–17CrossRef
74.
go back to reference Borghini A, Andreassi MG (2018) Genetic polymorphisms offer insight into the causal role of microRNA in coronary artery disease. Atherosclerosis. 269:63–70PubMedCrossRef Borghini A, Andreassi MG (2018) Genetic polymorphisms offer insight into the causal role of microRNA in coronary artery disease. Atherosclerosis. 269:63–70PubMedCrossRef
75.
go back to reference Guay C, Regazzi R (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 9(9):513CrossRefPubMed Guay C, Regazzi R (2013) Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 9(9):513CrossRefPubMed
76.
go back to reference Demirci MDS, Adan A (2020) Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection. bioRxiv Demirci MDS, Adan A (2020) Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection. bioRxiv
77.
go back to reference Lu D, Chatterjee S, Xiao K, Riedel I, Wang Y, Foo R et al (2020) MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes. J Mol Cell Cardiol 148:46–49PubMedPubMedCentralCrossRef Lu D, Chatterjee S, Xiao K, Riedel I, Wang Y, Foo R et al (2020) MicroRNAs targeting the SARS-CoV-2 entry receptor ACE2 in cardiomyocytes. J Mol Cell Cardiol 148:46–49PubMedPubMedCentralCrossRef
78.
go back to reference Li H, Zi P, Shi H, Gao M, Sun R (2018) Role of signaling pathway of long non-coding RNA growth arrest-specific transcript 5/microRNA-200c-3p/angiotensin converting enzyme 2 in the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome. Zhonghua Yi Xue Za Zhi 98(41):3354–3359PubMed Li H, Zi P, Shi H, Gao M, Sun R (2018) Role of signaling pathway of long non-coding RNA growth arrest-specific transcript 5/microRNA-200c-3p/angiotensin converting enzyme 2 in the apoptosis of human lung epithelial cell A549 in acute respiratory distress syndrome. Zhonghua Yi Xue Za Zhi 98(41):3354–3359PubMed
79.
go back to reference Li W, Wang R (2017) Ma J-y, Wang M, Cui J, Wu W-b, et al. A human long non-coding RNA ALT1 controls the cell cycle of vascular endothelial cells via ACE2 and cyclin D1 pathway. Cell Physiol Biochem 43(3):1152–1167PubMedCrossRef Li W, Wang R (2017) Ma J-y, Wang M, Cui J, Wu W-b, et al. A human long non-coding RNA ALT1 controls the cell cycle of vascular endothelial cells via ACE2 and cyclin D1 pathway. Cell Physiol Biochem 43(3):1152–1167PubMedCrossRef
80.
go back to reference Nersisyan S, Shkurnikov M, Turchinovich A, Knyazev E, Tonevitsky A (2020) Integrative analysis of miRNA and mRNA sequencing data reveals potential regulatory mechanisms of ACE2 and TMPRSS2. PLoS One 15(7):e0235987PubMedPubMedCentralCrossRef Nersisyan S, Shkurnikov M, Turchinovich A, Knyazev E, Tonevitsky A (2020) Integrative analysis of miRNA and mRNA sequencing data reveals potential regulatory mechanisms of ACE2 and TMPRSS2. PLoS One 15(7):e0235987PubMedPubMedCentralCrossRef
81.
go back to reference Lambert DW, Lambert LA, Clarke NE, Hooper NM, Porter KE, Turner AJ (2014) Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421. Clin Sci 127(4):243–249CrossRef Lambert DW, Lambert LA, Clarke NE, Hooper NM, Porter KE, Turner AJ (2014) Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421. Clin Sci 127(4):243–249CrossRef
82.
go back to reference Trojanowicz B, Imdahl T, Ulrich C, Fiedler R, Girndt M (2019) Circulating miR-421 targeting leucocytic angiotensin converting enzyme 2 is elevated in patients with chronic kidney disease. Nephron. 141(1):61–74PubMedCrossRef Trojanowicz B, Imdahl T, Ulrich C, Fiedler R, Girndt M (2019) Circulating miR-421 targeting leucocytic angiotensin converting enzyme 2 is elevated in patients with chronic kidney disease. Nephron. 141(1):61–74PubMedCrossRef
83.
go back to reference Zhang R, Su H, Ma X, Xu X, Liang L, Ma G et al (2019) MiRNA let-7b promotes the development of hypoxic pulmonary hypertension by targeting ACE2. Am J Phys Lung Cell Mol Phys 316(3):L547–LL57 Zhang R, Su H, Ma X, Xu X, Liang L, Ma G et al (2019) MiRNA let-7b promotes the development of hypoxic pulmonary hypertension by targeting ACE2. Am J Phys Lung Cell Mol Phys 316(3):L547–LL57
84.
go back to reference Fernandes T, Hashimoto NY, Magalhães FC, Fernandes FB, Casarini DE, Carmona AK et al (2011) Aerobic exercise training–induced left ventricular hypertrophy involves regulatory MicroRNAs, decreased angiotensin-converting enzyme-angiotensin II, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1-7). Hypertension. 58(2):182–189PubMedCrossRef Fernandes T, Hashimoto NY, Magalhães FC, Fernandes FB, Casarini DE, Carmona AK et al (2011) Aerobic exercise training–induced left ventricular hypertrophy involves regulatory MicroRNAs, decreased angiotensin-converting enzyme-angiotensin II, and synergistic regulation of angiotensin-converting enzyme 2-angiotensin (1-7). Hypertension. 58(2):182–189PubMedCrossRef
85.
go back to reference Huang Y, Zhang Y, Liu C, Huang J, Ding G (2016) microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme 2. Eur Rev Med Pharmacol Sci 20(19):4055PubMed Huang Y, Zhang Y, Liu C, Huang J, Ding G (2016) microRNA-125b contributes to high glucose-induced reactive oxygen species generation and apoptosis in HK-2 renal tubular epithelial cells by targeting angiotensin-converting enzyme 2. Eur Rev Med Pharmacol Sci 20(19):4055PubMed
86.
go back to reference Goyal R, Van-Wickle J, Goyal D, Longo LD (2015) Antenatal maternal low protein diet: ACE-2 in the mouse lung and sexually dimorphic programming of hypertension. BMC Physiol 15(1):2PubMedPubMedCentralCrossRef Goyal R, Van-Wickle J, Goyal D, Longo LD (2015) Antenatal maternal low protein diet: ACE-2 in the mouse lung and sexually dimorphic programming of hypertension. BMC Physiol 15(1):2PubMedPubMedCentralCrossRef
87.
go back to reference Wang Y, Lumbers ER, Arthurs AL (2018) Corbisier de Meaultsart C, Mathe A, Avery-Kiejda KA, et al. Regulation of the human placental (pro) renin receptor-prorenin-angiotensin system by microRNAs. MHR: Basic Sci Reprod Med 24(9):453–464 Wang Y, Lumbers ER, Arthurs AL (2018) Corbisier de Meaultsart C, Mathe A, Avery-Kiejda KA, et al. Regulation of the human placental (pro) renin receptor-prorenin-angiotensin system by microRNAs. MHR: Basic Sci Reprod Med 24(9):453–464
88.
go back to reference Rizzo P, Dalla Sega FV, Fortini F, Marracino L, Rapezzi C, Ferrari R (2020) COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm? Basic Res Cardiol 115(3) Rizzo P, Dalla Sega FV, Fortini F, Marracino L, Rapezzi C, Ferrari R (2020) COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm? Basic Res Cardiol 115(3)
89.
go back to reference Chen Y, Shan K, Qian W (2020) Asians do not exhibit elevated expression or unique genetic polymorphisms for ACE2, the cell-entry receptor of SARS-CoV-2. Preprints Chen Y, Shan K, Qian W (2020) Asians do not exhibit elevated expression or unique genetic polymorphisms for ACE2, the cell-entry receptor of SARS-CoV-2. Preprints
Metadata
Title
Epigenetic alterations and genetic variations of angiotensin-converting enzyme 2 (ACE2) as a functional receptor for SARS-CoV-2: potential clinical implications
Authors
Anvarsadat Kianmehr
Isabella Faraoni
Omer Kucuk
Abdolkarim Mahrooz
Publication date
01-08-2021
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 8/2021
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-021-04264-9

Other articles of this Issue 8/2021

European Journal of Clinical Microbiology & Infectious Diseases 8/2021 Go to the issue