Genetic Susceptibility to Coronavirus Disease 19 (COVID-19): A Review
Keywords:
COVID-19, Gene, Immune system, Susceptibility, X-chromosome.Abstract
Background: Certain gene polymorphisms are suspected to contribute to the geographic-specific susceptibility of people to coronavirus disease 19 (COVID-19), which may be used as therapeutic targets. Accordingly, this review articulates suspected COVID-19 susceptibility genes to assist researchers and medical practitioners to formulate effective drug and treatment procedure.
Method: Reputable electronic academic databases, including PubMed, Springer Link, and Scopus were searched for relevant information on the subject.
Results and Discussion: The search identified seven COVID-19 susceptibility genes, which are TICAM2, TLRs, ACE, ABO blood group gene, HLA, and TMPRSS2. Polymorphisms in ACE and TMPRSS2 may increase or decrease the binding of the virus to the human cell, while polymorphisms in TICAM2, TLRs, and HLA may enhance or compromise the immune system. Type O blood group seems to be the most protective ABO blood group because of its abundant antibodies and blood clothing inhibition, while type A blood group is the least protective. The distribution of the polymorphisms is influenced by geographical locations, which could contribute to the worldwide differential vulnerability of people to the disease. Most protective polymorphisms are prevalent among Africans and Asians, which could be the reason for their less susceptible to the disease compared to Europeans and Americans. Most genes reside on the X - chromosome, which could partly explain the dominance of the severe form of the disease among men than women.
Conclusion: Polymorphisms in certain genes may modulate COVID-19 infectivity and severity. A thorough understanding of the biological mechanisms of these genes may help design a cure.
References
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37) Delanghe JR, Speeckaert MM, De Buyzere ML. The host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections. Clin Chim Acta. 2020; 505:192-193. doi: 10.1016/j.cca.2020.03.031.
38) Chan KA, Tang NL, Hui, DS, et al. Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study. BMC Infect Dis 2005; 5:26. https://doi.org/10.1186/1471-2334-5-26
39) Sanchez?Mazas A. HLA studies in the context of coronavirus outbreaks. Swiss Med Wkly, 2020; 150: w20248. DOI: https://doi.org/10.4414/smw.2020.20248.
40) Debnath M, Banerjee M, Berk M. Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes. FASEB J. 2020 (Ahead of print). doi: 10.1096/fj.202001115R.
41) González?Galarza F, Takeshita L, Santos E, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015;43: D784?D788. doi: 10.1093/nar/gku1166.
42) Allele Frequency Databases (AFND) (2020). Allele Frequency in Worldwide Population. http://www.allelefrequencies.net/hla6006a.asp. (Accessed on June 20, 2020).
43) Zahn LM. HLA genetics and COVID-19. Science, 2020; 368 (6493: 841. DOI: 10.1126/science.368.6493.841-b
44) Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, 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. doi: 10.1016/j.cell.2020.02.052.
45) Irham LM, Chou W-H, Calkins MJ, Adikusuma W, Shie-LiangHsieh S-L, Chang W-C. Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression among population cohorts from multiple continents. Biochemical and Biophysical Research Communications, 2020; 529 (2): 263-269. https://doi.org/10.1016/j.bbrc.2020.05.179
46) Bertram S, Heurich A, Lavender H, et al. Influenza and SARS coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts. PLoS One. 2012;7 (4):e35876. https://doi.org/10.1371/journal.pone.0035876.
47) Maya EAL, van der Graaf A, Lanting P, van der Geest M, Fu J, Swertz M, et al. Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes. Front. Genet., 2020; 11:613. https://doi.org/10.3389/fgene.2020.00613
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49) Stopsack KH, Mucci LA, Antonarakis ES, Nelson PS, Kantoff PW. TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention? Cancer Discov 2020; 10 (6):779–82. DOI: 10.1158/2159-8290.CD-20-0451.
50) Hatesuer B, Bertram S, Mehnert N, Bahgat MM, Nelson PS, Pohlmann S, et al. Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice. PLoS Pathog 2013;9:e1003774. DOI: 10.1371/journal.ppat.1003774.
2) Coronaviridae Study Group of the ICTV. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020;5:236–544. doi: 10.1038/s41564-020-0695-z.
3) Peng Z, Xing-Lou Y, Xian-Guang W, Ben H, Lei Z, Wei Z, et al. A pneumonia outbreak associated with a new coronavirus of probable bat Origin. Nature. 2020;579(7798):270–273. DOI: 10.1038/s41586-020-2012-7
4) Lu R, Zhao X, Li J, Niu P, Yang B, Wu H. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020;395(10224):565–574. DOI: 10.1016/S0140-6736(20)30251-8.
5) Sironi M, Hasnain SE, Rosenthal B, Phan T, Luciani F, Shaw MA, et al. 2020. SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective. Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases, 2020; 84:104384. DOI: 10.1016/j.meegid.2020.104384.
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10) Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, et al. Human leukocyte antigen susceptibility map for severe acute respiratory syndrome coronavirus 2. J Virol 2020; 94:e00510-20. https://doi .org/10.1128/JVI.00510-20.
11) Nguyen A, Nello A, Thompson R. (2020). Your genes could determine whether the coronavirus puts you in the hospital – and we’re starting to unravel which ones matter. The Conversation-Academic rigour journalistic fair. Available at https://theconversation.com/your-genes-could-determine-whether-the-coronavirus-puts-you-in-the-hospital-and-were-starting-to-unravel-which-ones-matter-137145
12) Darbeheshti F, Rezaei N. Genetic predisposition models to COVID-19 infection. Med Hypotheses. 2020 6;142:109818. doi: 10.1016/j.mehy.2020.109818.
13) Mangin L (2020). Do Your Genes Predispose You to COVID-19? Scientific America. Available at https://www.scientificamerican.com/article/do-your-genes-predispose-you-to-covid-19/ (Accessed June 11, 2020).
14) Georgel P, Macquin C, Bahram S. The Heterogeneous Allelic Repertoire of Human Toll-Like Receptor (TLR) Genes. PLoS ONE, 2009; 4(11): e7803. https://doi.org/10.1371/journal.pone.0007803
15) Immune Deficiency Foundation (2020). Innate Immune Defects. Available at https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/innate-immune-defects.
16) Mazaleuskaya L, Veltrop R, Ikpeze N, Martin-Garcia J, Navas-Martin S. Protective role of Toll-like Receptor 3-induced type I interferon in murine coronavirus infection of macrophages. Viruses, 2012; 4(5):901-23. doi: 10.3390/v4050901.
17) Gralinski LE, Menachery VD, Morgan AP, Totura AL, Beall A, Kocher J, et al. Allelic Variation in the Toll-Like Receptor Adaptor Protein Ticam2 Contributes to SARS-Coronavirus Pathogenesis in Mice. G3, 2017; 7: 1653-1663. https://doi.org/10.1534/g3.117.041434
18) Katsnelson A (2020). Genetic study suggests that people’s blood type may affect their COVID-19 risk. c&en, 98 (23). Available at https://cen.acs.org/biological-chemistry/infectious-disease/Genetic-study-suggests-peoples-blood/98/i23.
19) Cheng Y, Cheng G, Chui C, Lau YF, Chan PKS, Margaret NHL, et al. ABO Blood Group and Susceptibility to Severe Acute Respiratory Syndrome. JAMA. 2005;293(12):1447-1451. doi:10.1001/jama.293.12.1450-c.
20) Guillon P, Clément M, Sébille V, Rivain J-G, Chou C-F, Ruvoën-Clouet N, et al. Inhibition of the interaction between the SARS-CoV Spike protein and its cellular receptor by anti-histo-blood group antibodies, Glycobiology, 2008; 18 (12): 1085–1093, https://doi.org/10.1093/glycob/cwn093
21) Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, et al. The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis. medRxiv, (preprint). doi: https://doi.org/10.1101/2020.05.31.20114991.
22) Li J, Wang X, Chen J, CaiY, Deng A, Yang M. .Association between ABO blood groups and risk of SARS?CoV?2 pneumonia. British Journal of Haematology, 2020; 1-4. https://doi.org/10.1111/bjh.16797.
23) Yancy CW. COVID?19 and African Americans. JAMA, 2020; 323 (19):1891–1892. DOI: 10.1001/jama.2020.6548.
24) Genetics Home Reference. ACE gene.https://ghr.nlm.nih.gov/gene/ACE
25) Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discovery, 2020; 6(1):1–4.DOI: 10.1038/s41421-020-0147-1.
26) Devaux CA, Rolain J-M, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. Journal of Microbiology, Immunology and Infection, 2020; 53 (3): 425-435. https://doi.org/10.1016/j.jmii.2020.04.015.
27) Calcagnile M, Forgez P, Iannelli A, Bucci C, Alifano M, Alifano P. ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study. bioRxiv (preprint) doi: https://doi.org/10.1101/2020.04.23.057042
28) Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 2012; 4: 1011-1033. DOI:10.3390/v4061011
29) Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181 (2): 281-292.e6 (2020).DOI : 10.1016/j.cell.2020.02.058.
30) Wrapp D, Wang N, Corbett KS, Goldsmith AJ, Hsieh A-L, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020; 367: 1260-1263. DOI:10.1126/science.abb2507
31) Stawiski EW, Diwanji D, Suryamohan K, Gupta R, Fellouse FA, Sathirapongsasuti JF, et al. Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility. bioRxiv 2020 (preprint). doi: https://doi.org/10.1101/2020.04.07.024752
32) Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J BiolChem, 2000; 275:33238-33243. doi: 10.1074/jbc.M002615200.
33) Cirulli ET, Riffle S, Bolze A, Washington NL. Revealing variants in SARS-CoV-2 interaction domain of ACE2 and loss of function intolerance through analysis of >200,000 exomes. bioRxiv 2020 (preprint). doi: https://doi.org/10.1101/2020.04.07.030544
34) Hussain M, Jabeen N, Raza F, Shabbir S, Baig AA, Amanullah A, et al. Structural variations in human ACE2 may influence its binding with SARS?CoV?2 spike protein. Journal of Medical Virology, 2020.https://doi.org/10.1002/jmv.25832
35) Cai H. Sex difference and smoking predisposition in patients with COVID-19.Lancet Respir Med. 2020; 8(4):e20 DOI: 10.1016/S2213-2600(20)30117-X.
36) Alifano M, Alifano P, Forgez P, Iannelli A. Renin-angiotensin system at the heart of COVID-19 pandemic.Biochimie 2020; 174:30-33. DOI: 10.1016/j.biochi.2020.04.008.
37) Delanghe JR, Speeckaert MM, De Buyzere ML. The host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections. Clin Chim Acta. 2020; 505:192-193. doi: 10.1016/j.cca.2020.03.031.
38) Chan KA, Tang NL, Hui, DS, et al. Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study. BMC Infect Dis 2005; 5:26. https://doi.org/10.1186/1471-2334-5-26
39) Sanchez?Mazas A. HLA studies in the context of coronavirus outbreaks. Swiss Med Wkly, 2020; 150: w20248. DOI: https://doi.org/10.4414/smw.2020.20248.
40) Debnath M, Banerjee M, Berk M. Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes. FASEB J. 2020 (Ahead of print). doi: 10.1096/fj.202001115R.
41) González?Galarza F, Takeshita L, Santos E, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015;43: D784?D788. doi: 10.1093/nar/gku1166.
42) Allele Frequency Databases (AFND) (2020). Allele Frequency in Worldwide Population. http://www.allelefrequencies.net/hla6006a.asp. (Accessed on June 20, 2020).
43) Zahn LM. HLA genetics and COVID-19. Science, 2020; 368 (6493: 841. DOI: 10.1126/science.368.6493.841-b
44) Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, 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. doi: 10.1016/j.cell.2020.02.052.
45) Irham LM, Chou W-H, Calkins MJ, Adikusuma W, Shie-LiangHsieh S-L, Chang W-C. Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression among population cohorts from multiple continents. Biochemical and Biophysical Research Communications, 2020; 529 (2): 263-269. https://doi.org/10.1016/j.bbrc.2020.05.179
46) Bertram S, Heurich A, Lavender H, et al. Influenza and SARS coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts. PLoS One. 2012;7 (4):e35876. https://doi.org/10.1371/journal.pone.0035876.
47) Maya EAL, van der Graaf A, Lanting P, van der Geest M, Fu J, Swertz M, et al. Lack of Association Between Genetic Variants at ACE2 and TMPRSS2 Genes Involved in SARS-CoV-2 Infection and Human Quantitative Phenotypes. Front. Genet., 2020; 11:613. https://doi.org/10.3389/fgene.2020.00613
48) dos Santos NPC, Khayat AS, Rodrigues JCG , Pinto P, de Araújo GS, Pastana LF, et al. TMPRSS2 variants and their susceptibility to COVID-19: focus in East Asian and European populations. medRxiv (preprint), https://doi.org/10.1101/2020.06.09.20126680
49) Stopsack KH, Mucci LA, Antonarakis ES, Nelson PS, Kantoff PW. TMPRSS2 and COVID-19: Serendipity or Opportunity for Intervention? Cancer Discov 2020; 10 (6):779–82. DOI: 10.1158/2159-8290.CD-20-0451.
50) Hatesuer B, Bertram S, Mehnert N, Bahgat MM, Nelson PS, Pohlmann S, et al. Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice. PLoS Pathog 2013;9:e1003774. DOI: 10.1371/journal.ppat.1003774.
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2021-06-23
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Yahaya, T., Oladele, E., Nnochiri, K., Abdullahi, H., & Nathaniel, J. (2021). Genetic Susceptibility to Coronavirus Disease 19 (COVID-19): A Review. Translation: The University of Toledo Journal of Medical Sciences, 9(1). Retrieved from https://openjournals.utoledo.edu/index.php/translation/article/view/408
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