Association of angiotensin-converting enzyme 2 gene (rs1514283) polymorphism with the incidence of COVID-19

Main Article Content

Hams Hussain Hashim Al-Fattli
Tabarek Salam Abd-Alraoof


ACE2, rs1514283 SNP, COVID-19, Hypertension


It has been a busy year for coronaviruses, with the most recent one causing severe coronavirus illness in 2019 (COVID-19). It is broadly distributed in many human tissues and organs as the potential SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2). ACE2 provides homeostatic modulation of circulation angiotensin II levels by acting as a physiological counterbalance to ACE. They have been linked to COVID-19 disease acquisition, progression, and severity. As a result, we investigated how ACE2 variations and epigenetic variables affect SARS-CoV-2 infection susceptibility and infection outcomes in terms of age, gender and ethnicity. Debates raged over an etiology of this occurrence. It is important to note that further research is required to demonstrate the efficacy of human recombinant ACE2 and ACE2-derived peptides in fighting SARSCoV-2 variants. A better recognition of a host genetic as well as the function of the proerties of ACE2 variations would assist in explaining clinical disparities of infection between individuals and contributing in development of remedies and managing future SARS-CoV-2 epidemics, an essential function for ACE2 in Essential Hypertension (EH). We wanted to see how ACE2 gene polymorphisms and enzyme activity correlated with COVID-19 incidence in the Iraqi province of Al-Diwaniya! 63 COVID-19 patients and 70 (NT)controls were genotyped using Sequenom Mass-ARRAY RS1000 for ACE2. Participants' ACE2 rs1514283 SNP was linked to COVID-19.

Abstract 66 | PDF Downloads 48 XML Downloads 15 HTML Downloads 22


[1] S. Kulkarni, B. L. Jenner, and I. Wilkinson, "COVID-19 and hypertension,"J. renin-angiotensin-aldosterone Syst., vol. 21, no. 2, p. 1470320320927851, 2020.
[2] C. Gao et al., "Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study,"Eur. Heart J., vol. 41, no. 22, pp. 2058–2066, 2020.
[3] S.-A. Muhamad, A. Ugusman, J. Kumar, D. Skiba, A. A. Hamid, and A. Aminuddin, "COVID-19 and hypertension: the what, the why, and the how,"Front. Physiol., vol. 12, p. 589, 2021.
[4] M. Tadic, C. Cuspidi, G. Mancia, R. Dell'Oro, and G. Grassi, "COVID-19, hypertension and cardiovascular diseases: Should we change the therapy?,"Pharmacol. Res., vol. 158, p. 104906, 2020.
[5] E. L. Schiffrin, J. M. Flack, S. Ito, P. Muntner, and R. C. Webb, “Hypertension and COVID-19,” American journal of hypertension, vol. 33, no. 5. Oxford University Press US, pp. 373–374, 2020.
[6] G. Lippi, J. Wong, and B. M. Henry, "Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis,"Pol Arch Intern Med, vol. 130, no. 4, pp. 304–309, 2020.
[7] B. Möhlendick et al., "ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19,"Pharmacogenet. Genomics, 2021.
[8] A. S. Khayat et al., "ACE2 polymorphisms as potential players in COVID-19 outcome,"PLoS One, vol. 15, no. 12, p. e0243887, 2020.
[9] A. Paniri, M. M. Hosseini, M. Moballegh-Eslam, and H. Akhavan-Niaki, "Comprehensive in silico identification of impacts of ACE2 SNPs on COVID-19 susceptibility in different populations,"Gene reports, vol. 22, p. 100979, 2021.
[10] L. Fang, G. Karakiulakis, and M. Roth, "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?,"lancet Respir. Med., vol. 8, no. 4, p. e21, 2020.
[11] H. Singh, R. Choudhari, V. Nema, and A. A. Khan, "ACE2 and TMPRSS2 polymorphisms in various diseases with special reference to its impact on COVID-19 disease,"Microb. Pathog., vol. 150, p. 104621, 2021.
[12] R. Asselta, E. M. Paraboschi, A. Mantovani, and S. Duga, "ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy,"Aging (Albany NY), vol. 12, no. 11, p. 10087, 2020.
[13] S. Shibata et al., "Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19,"Hypertens. Res., vol. 43, no. 10, pp. 1028–1046, 2020.
[14] M. Chaudhary, "COVID-19 susceptibility: potential of ACE2 polymorphisms,"Egypt. J. Med. Hum. Genet., vol. 21, no. 1, pp. 1–8, 2020.
[15] N. Pouladi and S. Abdolahi, "Investigating the ACE2 polymorphisms in COVID‐19 susceptibility: An in silico analysis,"Mol. Genet. Genomic Med., vol. 9, no. 6, p. e1672, 2021.
[16] L. Wooster, C. J. Nicholson, H. H. Sigurslid, C. L. L. Cardenas, and R. Malhotra, "Polymorphisms in the ACE2 locus associate with severity of COVID-19 infection,"medRxiv, 2020.
[17] M. Hashizume, G. Gonzalez, C. Ono, A. Takashima, and M. Iwasaki, "Population-specific ACE2 single-nucleotide polymorphisms have limited impact on SARS-CoV-2 infectivity in vitro,"Viruses, vol. 13, no. 1, p. 67, 2021.
[18] M. Bosso, T. A. Thanaraj, M. Abu-Farha, M. Alanbaei, J. Abubaker, and F. Al-Mulla, "The two faces of ACE2: the role of ACE2 receptor and its polymorphisms in hypertension and COVID-19,"Mol. Ther. Clin. Dev., vol. 18, pp. 321–327, 2020.
[19] C. Savoia, M. Volpe, and R. Kreutz, "Hypertension, a moving target in COVID-19: current views and perspectives,"Circ. Res., vol. 128, no. 7, pp. 1062–1079, 2021.
[20] L. F. Drager, A. Pio-Abreu, R. D. Lopes, and L. A. Bortolotto, "Is hypertension a real risk factor for poor prognosis in the COVID-19 pandemic?,"Curr. Hypertens. Rep., vol. 22, no. 6, pp. 1–6, 2020.
[21] V. Bhalla, C. A. Blish, and A. M. South, "A historical perspective on ACE2 in the COVID-19 era,"J. Hum. Hypertens., vol. 35, no. 10, pp. 935–939, 2021.
[22] A. D. Melin, M. C. Janiak, F. Marrone, P. S. Arora, and J. P. Higham, "Comparative ACE2 variation and primate COVID-19 risk,"Commun. Biol., vol. 3, no. 1, pp. 1–9, 2020.
[23] A. M. South, D. I. Diz, and M. C. Chappell, "COVID-19, ACE2, and the cardiovascular consequences,"Am. J. Physiol. Circ. Physiol., 2020.
[24] Z. Leng et al., "Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia,"Aging Dis., vol. 11, no. 2, p. 216, 2020.
[25] H. Jia, E. Neptune, and H. Cui, "Targeting ACE2 for COVID-19 therapy: opportunities and challenges,"Am. J. Respir. Cell Mol. Biol., vol. 64, no. 4, pp. 416–425, 2021.
[26] Y. Jing et al., "Potential influence of COVID-19/ACE2 on the female reproductive system,"Mol. Hum. Reprod., vol. 26, no. 6, pp. 367–373, 2020.
[27] A. B. Patel and A. Verma, "Nasal ACE2 levels and COVID-19 in children,"Jama, vol. 323, no. 23, pp. 2386–2387, 2020.
[28] F. Chaudhry et al., "Manipulation of ACE2 expression in COVID-19,"Open Hear., vol. 7, no. 2, p. e001424, 2020.
[29] S. Suh et al., "A systematic review on papers that study on Single Nucleotide Polymorphism that affects coronavirus 2019 severity,"BMC Infect. Dis., vol. 22, no. 1, pp. 1–11, 2022.
[30] S. Suh et al., "A Systematic Review on Papers That Study on SNPs That Affect SARS-CoV-2 Infection & COVID-19 Severity," 2021.
[31] X. Zhang, S. Li, and S. Niu, "ACE2 and COVID-19 and the resulting ARDS,"Postgrad. Med. J., vol. 96, no. 1137, pp. 403–407, 2020.
[32] J. Sieńko et al., "COVID-19: the influence of ACE genotype and ACE-I and ARBs on the course of SARS-CoV-2 infection in elderly patients,"Clin. Interv. Aging, vol. 15, p. 1231, 2020.
[33] Ahmad Mohammed Alwan et al., "The impact of CYP19A1 variants and haplotypes on breast cancer risk, clinicopathological features and prognosis,"Mol. Genet. Genomic Med., vol. 9, no. 7, pp. 1–10, 2021, doi: 10.1002/mgg3.1705.
[34] L. M. Burrell, S. B. Harrap, E. Velkoska, and S. K. Patel, "The ACE2 gene: its potential as a functional candidate for cardiovascular disease,"Clin. Sci., vol. 124, no. 2, pp. 65–76, 2013.
[35] Y. Singh, G. Gupta, A. Mishra, D. K. Chellappan, and K. Dua, "Gender and age differences reveal risk patterns in COVID-19 outbreak,"Altern. Ther. Health Med., vol. 26, no. S2, pp. 54–55, 2020.
[36] D. Gemmati and V. Tisato, "Genetic hypothesis and pharmacogenetics side of renin-angiotensin-system in COVID-19,"Genes (Basel)., vol. 11, no. 9, p. 1044, 2020.