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Protein & Peptide Letters

Author(s): Anum Siraj, Saira Yahya*, Amber Khan and Saleem Awan

DOI: 10.2174/0929866530666221206094926

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ACE2 Receptor Polymorphism and its Correlation with Anti-SARS-CoV-2 IgM Antibodies - A Case-Control Study

Page: [146 - 153] Pages: 8

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Abstract

Background: The SARS-CoV-2 pandemic originated in Wuhan, China in December 2019 and spread rapidly worldwide. The virus gets entry into target cells via angiotensin-converting enzyme 2 (ACE2) receptors and its gene is highly polymorphic.

Introduction: The variations in SARS-CoV-2 susceptibility and severity can be explained on a genetic level by studying the polymorphism in ACE2 receptor polymorphism.

Objective: A prospective case-control study was designed to compare the ACE2 levels in SARS-CoV- 2 patients with the healthy controls in the local population, for which a total of 100 EDTA-containing blood samples were included (50 SARS-CoV-2 IgM positive case and 50 healthy controls).

Methods: PCR-RFLP was performed to investigate the polymorphism of ACE2 in genomic DNA and the ACE2 plasma levels were determined through ELISA.

Results: No significant difference in allelic and genotype frequencies (GG, GA, AA) were observed while the ACE2 plasma levels were found to be decreased in positive samples.

Conclusion: No significant association of the ACE2 gene polymorphism (G8790A) was found with the SARS-CoV-2 susceptibility in the Pakistani population which intimates the search for other genetic factors within the local population.

Graphical Abstract

[1]
Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G.F.; Tan, W. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med., 2020, 382(8), 727-733.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[2]
Waris, A.; Atta, U.K.; Ali, M.; Asmat, A.; Baset, A. COVID-19 outbreak: Current scenario of Pakistan. New Microbes New Infect., 2020, 35, , 100681..
[http://dx.doi.org/10.1016/j.nmni.2020.100681] [PMID: 32322403]
[3]
Dong, Y.; Mo, X.; Hu, Y.; Qi, X.; Jiang, F.; Jiang, Z.; Tong, S. Epidemiology of COVID-19 among children in China. Pediatrics, 2020, 145(6), , e20200702..
[http://dx.doi.org/10.1542/peds.2020-0702] [PMID: 32179660]
[4]
The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol., 2020, 5(4), 536-544.
[http://dx.doi.org/10.1038/s41564-020-0695-z] [PMID: 32123347]
[5]
Wu, Z.; McGoogan, J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China. JAMA, 2020, 323(13), 1239-1242.
[http://dx.doi.org/10.1001/jama.2020.2648] [PMID: 32091533]
[6]
Hou, Y.; Zhao, J.; Martin, W.; Kallianpur, A.; Chung, M.K.; Jehi, L.; Sharifi, N.; Erzurum, S.; Eng, C.; Cheng, F. New insights into genetic susceptibility of COVID-19: An ACE2 and TMPRSS2 polymorphism analysis. BMC Med., 2020, 18(1), 216.
[http://dx.doi.org/10.1186/s12916-020-01673-z] [PMID: 32664879]
[7]
Medina-Enríquez, M.M.; Lopez-León, S. ACE2: The molecular doorway to SARS-CoV-2. 2020, 10(1), 148.
[8]
Simões e Silva, A.C.; Teixeira, M.M. ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis. Pharmacol. Res., 2016, 107, 154-162.
[http://dx.doi.org/10.1016/j.phrs.2016.03.018] [PMID: 26995300]
[9]
Millet, J.K.; Whittaker, G.R. Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res., 2015, 202, 120-134.
[http://dx.doi.org/10.1016/j.virusres.2014.11.021] [PMID: 25445340]
[10]
Zhou, F.; Yu, T.; Du, R.; Fan, G.; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; Guan, L.; Wei, Y.; Li, H.; Wu, X.; Xu, J.; Tu, S.; Zhang, Y.; Chen, H.; Cao, B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet, 2020, 395(10229), 1054-1062.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[11]
Yi, L.; Gu, Y.H.; Wang, X.L.; An, L.Z.; Xie, X.D.; Shao, W.; Ma, L.Y.; Fang, J.R.; An, Y.D.; Wang, F.; Zhang, D.L. Association of ACE, ACE2 and UTS2 polymorphisms with essential hypertension in Han and Dongxiang populations from north-western China. J. Int. Med. Res., 2006, 34(3), 272-283.
[http://dx.doi.org/10.1177/147323000603400306] [PMID: 16866021]
[12]
Chen, Q.; Tang, X.; Yu, C.Q.; Chen, D.F.; Tian, J.; Cao, Y.; Fan, W.Y.; Cao, W.H.; Zhan, S.Y.; Lv, J.; Guo, X.X.; Li, L.M.; Hu, Y.H. Correlation of angiotensin-converting enzyme 2 gene polymorphism with antihypertensive effects of benazepril. Beijing Da Xue Xue Bao, 2010, 42(3), 293-298.
[PMID: 20559404]
[13]
Patnaik, M.; Pati, P.; Swain, S.N.; Mohapatra, M.K.; Dwibedi, B.; Kar, S.K.; Ranjit, M. Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha, India. Ann. Hum. Biol., 2014, 41(2), 145-152.
[http://dx.doi.org/10.3109/03014460.2013.837195] [PMID: 24112034]
[14]
Pinheiro, D.S.; Santos, R.S.; Jardim, P.C.B.V.; Silva, E.G.; Reis, A.A.S.; Pedrino, G.R.; Ulhoa, C.J. The combination of ACE I/D and ACE2 G8790A polymorphisms revels susceptibility to hypertension: A genetic association study in Brazilian patients. PLoS One, 2019, 14(8), , e0221248..
[http://dx.doi.org/10.1371/journal.pone.0221248] [PMID: 31430320]
[15]
Zhou, J.B.; Yang, J.K. Meta-analysis of association of ACE2 G8790A polymorphism with Chinese Han essential hypertension. J. Renin Angiotensin Aldosterone Syst., 2009, 10(1), 31-34.
[http://dx.doi.org/10.1177/1470320309103047] [PMID: 19286756]
[16]
Malard, L.; Kakinami, L.; O’Loughlin, J.; Roy-Gagnon, M.H.; Labbe, A.; Pilote, L.; Hamet, P.; Tremblay, J.; Paradis, G. The association between the angiotensin-converting enzyme-2 gene and blood pressure in a cohort study of adolescents. BMC Med. Genet., 2013, 14(1), 117.
[http://dx.doi.org/10.1186/1471-2350-14-117] [PMID: 24191856]
[17]
Wu, Y.H.; Li, J.Y.; Wang, C.; Zhang, L.M.; Qiao, H. The ACE2 G8790A polymorphism: involvement in type 2 diabetes mellitus combined with cerebral stroke. J. Clin. Lab. Anal., 2017, 31(2), , e22033..
[http://dx.doi.org/10.1002/jcla.22033] [PMID: 27500554]
[18]
Cao, Y.; Li, L.; Feng, Z.; Wan, S.; Huang, P.; Sun, X.; Wen, F.; Huang, X.; Ning, G.; Wang, W. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov., 2020, 6(1), 11.
[http://dx.doi.org/10.1038/s41421-020-0147-1] [PMID: 32133153]
[19]
Li, W.; Zhang, C.; Sui, J.; Kuhn, J.H.; Moore, M.J.; Luo, S.; Wong, S.K.; Huang, I.C.; Xu, K.; Vasilieva, N.; Murakami, A.; He, Y.; Marasco, W.A.; Guan, Y.; Choe, H.; Farzan, M. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J., 2005, 24(8), 1634-1643.
[http://dx.doi.org/10.1038/sj.emboj.7600640] [PMID: 15791205]
[20]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. 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.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[21]
Saab, Y.B.; Gard, P.R.; Overall, A.D.J. The geographic distribution of the ACE II genotype: a novel finding. Genet. Res., 2007, 89(4), 259-267.
[http://dx.doi.org/10.1017/S0016672307009019] [PMID: 18208631]
[22]
Sabir, J.S.M.; Omri, A.E.; Ali Khan, I.; Banaganapalli, B.; Hajrah, N.H.; Zrelli, H.; Omar, A.M.S.; Alharbi, M.G.; Alhebshi, A.M.; Jansen, R.K.; Altaf, A.; Shaik, N.A.; Khan, M. ACE insertion/deletion genetic polymorphism, serum ACE levels and high dietary salt intake influence the risk of obesity development among the Saudi adult population. J. Renin Angiotensin Aldosterone Syst., 2019, 20(3), , 1470320319870945..
[http://dx.doi.org/10.1177/1470320319870945]
[23]
Hofmann, H.; Geier, M.; Marzi, A.; Krumbiegel, M.; Peipp, M.; Fey, G.H.; Gramberg, T.; Pöhlmann, S. Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor. Biochem. Biophys. Res. Commun., 2004, 319(4), 1216-1221.
[http://dx.doi.org/10.1016/j.bbrc.2004.05.114] [PMID: 15194496]
[24]
Li, Y. Lack of Association of ACE2 G8790A Gene Mutation with Essential Hypertension in the Chinese Population: A Meta-Analysis Involving 5260 Subjects. Front. Physiol., 2012, 3, 364.
[http://dx.doi.org/10.3389/fphys.2012.00364] [PMID: 22988445]
[25]
Foffa, I.; Murzi, M.; Mariani, M.; Mazzone, A.; Glauber, M.; Ait Ali, L.; Andreassi, M.G. Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves. J. Thorac. Cardiovasc. Surg., 2012, 144(2), 390-395.
[http://dx.doi.org/10.1016/j.jtcvs.2011.12.038]
[26]
Swärd, P.; Edsfeldt, A.; Reepalu, A.; Jehpsson, L.; Rosengren, B.E.; Karlsson, M.K. Age and sex differences in soluble ACE2 may give insights for COVID-19. Critical Care, 2020, 24(1), 221.
[http://dx.doi.org/10.1186/s13054-020-02942-2]