[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Journal Information::
Articles archive::
For Authors::
For Reviewers::
Contact us::
Site Facilities::
Search in website

Advanced Search
Receive site information
Enter your Email in the following box to receive the site news and information.
:: Volume 32, Issue 4 (winter 2022) ::
MEDICAL SCIENCES 2022, 32(4): 337-346 Back to browse issues page
Review on the role of host genetic factors in the susceptibility to SARS-CoV-2
Fatemeh Karami1 , Mohammad Hossein Modarressi 2
1- Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
2- Department of Medical Genetics, Faculty of Medicine, Tehran University Of Medical Sciences, Tehran, Iran , modaresi@tums.ac.ir
Abstract:   (826 Views)
Background: Severe acute respiratory system Cov-2 pandemic has affected the world populations for more than one year. Different incidence and severity of this viral disease among various age range and individuals with different background disease may indicate the pivotal role of host genetic factors in their prevalence and mortality rate. In this regards, present study was performed to review the most important genetic variants and factors in incidence and severity of SARS-CoV-2 based on the carried out studies in various populations.  
Materials and methods: Databases including PubMed, PubMed Central, Google Scholar, Bing, medRxiv and COVID-19 host genetics initiative were explored using key words including gene polymorphism, gene expression, gene variant, infection risk and disease severity to find the papers regarding genetic factors association with SARS-CoV-2 and its severity.
Results and Conclusion: Its seems that in addition to the HLA system variants and the genes related to interferons as well as IFITM3, ACE2, TMPRSS2, CD147, ACE and TLR7 genes are the most important genes which are involved in SARS-CoV-2 pathogenesis. Investigating the association of the most important genetic variants among different populations with SARS-Cov-2 can provide the way towards more targeted therapies for this disease. Moreover, by recognizing those variants, more efficient steps can be taken in early identification of the high risk carriers of the same next generation viruses.
Keywords: SARS-CoV-2, Gene variant, Gene polymorphism, Disease severity
Full-Text [PDF 328 kb]   (400 Downloads)    
Semi-pilot: Review | Subject: Genetic
Received: 2022/03/7 | Accepted: 2022/09/4 | Published: 2022/10/2
1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet 2020;395:1054-1062. [DOI:10.1016/S0140-6736(20)30566-3]
2. Sun P, Lu X, Xu C, Sun W, Pan B. Understanding of COVID-19 based on current evidence. Journal of medical virology 2020;92:548-551. [DOI:10.1002/jmv.25722]
3. Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020;215:108427. [DOI:10.1016/j.clim.2020.108427]
4. Ikitimur H, Borku Uysal B, Cengiz M, Ikitimur B, Uysal H, Ozcan E, et al. ''Determining Host Factors Contributing to Disease Severity in a Family Cluster of 29 Hospitalized SARS-CoV-2 Patients: Could Genetic Factors Be Relevant in the Clinical Course of COVID-19?''. Journal of medical virology 2020. [DOI:10.1002/jmv.26106]
5. Yousefzadegan S, Rezaei N. Case Report: Death due to COVID-19 in Three Brothers. Am J Trop Med Hyg 2020;102:1203-1204. [DOI:10.4269/ajtmh.20-0240]
6. LoPresti M, Beck DB, Duggal P, Cummings DAT, Solomon BD. The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature. The American Journal of Human Genetics 2020. [DOI:10.1101/2020.05.30.20117788]
7. Zhang Y, Qin L, Zhao Y, Zhang P, Xu B, Li K, et al. Interferon-Induced Transmembrane Protein 3 Genetic Variant rs12252-C Associated With Disease Severity in Coronavirus Disease 2019. J Infect Dis 2020;222:34-37. [DOI:10.1093/infdis/jiaa224]
8. Nikoloudis DK, Dimitrios; Hiona, Asimina. The Frequency of Combined IFITM3 Haplotype Involving the Reference Alleles of Both rs12252 and rs34481144 is in Line with COVID-19 Standardized Mortality Ratio of Ethnic Groups in England. 2020;2020050273. [DOI:10.20944/preprints202005.0273.v1]
9. Kim YC, Jeong BH. Strong Correlation between the Case Fatality Rate of COVID-19 and the rs6598045 Single Nucleotide Polymorphism (SNP) of the Interferon-Induced Transmembrane Protein 3 (IFITM3) Gene at the Population-Level. Genes 2020;12. [DOI:10.3390/genes12010042]
10. Hachim MY, Al Heialy S, Hachim IY, Halwani R, Senok AC, Maghazachi AA, et al. Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells. Frontiers in immunology 2020;11:1372. [DOI:10.3389/fimmu.2020.01372]
11. Sardar R, Satish D, Birla S, Gupta D. Integrative analyses of SARS-CoV-2 genomes from different geographical locations reveal unique features potentially consequential to host-virus interaction, pathogenesis and clues for novel therapies. Heliyon 2020:e04658. [DOI:10.1101/2020.03.21.001586]
12. Zhao X, Sehgal M, Hou Z, Cheng J, Shu S, Wu S, et al. Identification of Residues Controlling Restriction versus Enhancing Activities of IFITM Proteins on Entry of Human Coronaviruses. Journal of virology 2018;92. [DOI:10.1128/JVI.01535-17]
13. Tomita Y, Ikeda T, Sato R, Sakagami T. Association between HLA gene polymorphisms and mortality of COVID-19: An in silico analysis. Immunity, inflammation and disease 2020;8:684-694. [DOI:10.1002/iid3.358]
14. Arslan H, Musabak U, Ayvazoglu Soy EH, Kurt Azap O, Sayin B, Akcay S, et al. Incidence and Immunologic Analysis of Coronavirus Disease (COVID-19) in Hemodialysis Patients:A Single-Center Experience. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 2020;18:275-283. [DOI:10.6002/ect.2020.0194]
15. Poulton K, Wright P, Hughes P, Savic S, Welberry Smith M, Guiver M, et al. A role for human leucocyte antigens in the susceptibility to SARS-Cov-2 infection observed in transplant patients. International journal of immunogenetics 2020;47:324-328. [DOI:10.1111/iji.12505]
16. Amoroso A, Magistroni P, Vespasiano F, Bella A, Bellino S, Puoti F, et al. HLA and AB0 Polymorphisms May Influence SARS-CoV-2 Infection and COVID-19 Severity. Transplantation 2021;105:193-200. [DOI:10.1097/TP.0000000000003507]
17. Pisanti S, Deelen J, Gallina AM, Caputo M, Citro M, Abate M, et al. Correlation of the two most frequent HLA haplotypes in the Italian population to the differential regional incidence of Covid-19. Journal of translational medicine 2020;18:352. [DOI:10.1186/s12967-020-02515-5]
18. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods in molecular biology (Clifton, NJ) 2015;1282:1-23. [DOI:10.1007/978-1-4939-2438-7_1]
19. Li F. Receptor recognition and cross-species infections of SARS coronavirus. Antiviral research 2013;100:246-254. [DOI:10.1016/j.antiviral.2013.08.014]
20. Benetti E, Tita R, Spiga O, Ciolfi A, Birolo G, Bruselles A, et al. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. European journal of human genetics : EJHG 2020;28:1602-1614. [DOI:10.1038/s41431-020-0691-z]
21. Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations.
22. Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V. COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males? International journal of molecular sciences 2020;21. [DOI:10.3390/ijms21103474]
23. Lippi G, Lavie CJ, Henry BM, Sanchis-Gomar F. Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)? Clinical chemistry and laboratory medicine 2020;58:1415-1422. [DOI:10.1515/cclm-2020-0727]
24. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science (New York, NY) 2004;303:1526-1529. [DOI:10.1126/science.1093620]
25. 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. [DOI:10.1002/jmv.25832]
26. Procko E. The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2. bioRxiv : the preprint server for biology 2020. [DOI:10.1101/2020.03.16.994236]
27. Stawiski EW, Diwanji D, Suryamohan K, Gupta R, Fellouse FA, Sathirapongsasuti JF, et al. Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility. bioRxiv : the preprint server for biology 2020:2020.2004.2007.024752. [DOI:10.1101/2020.04.07.024752]
28. Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pöhlmann S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. Journal of virology 2014;88:1293-1307. [DOI:10.1128/JVI.02202-13]
29. Al-Mulla F, Mohammad A, Al Madhoun A, Haddad D, Ali H, Eaaswarkhanth M, et al. A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine. bioRxiv : the preprint server for biology 2020:2020.2005.2016.099176. [DOI:10.1101/2020.05.16.099176]
30. Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, et al. An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer cell 2010;17:443-454. [DOI:10.1016/j.ccr.2010.03.018]
31. Schuler BA, Habermann AC, Plosa EJ, Taylor CJ, Jetter C, Kapp ME, et al. Age-related expression of SARS-CoV-2 priming protease TMPRSS2 in the developing lung. bioRxiv : the preprint server for biology 2020.
32. Bhattacharyya C, Das C, Ghosh A, Singh AK, Mukherjee S, Majumder PP, et al. Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes. bioRxiv : the preprint server for biology 2020:2020.2005.2004.075911. [DOI:10.1101/2020.05.04.075911]
33. Russo R, Andolfo I, Lasorsa VA, Iolascon A, Capasso M. Genetic Analysis of the Coronavirus SARS-CoV-2 Host Protease TMPRSS2 in Different Populations. Frontiers in genetics 2020;11:872. [DOI:10.3389/fgene.2020.00872]
34. Torre-Fuentes L, Matías-Guiu J, Hernández-Lorenzo L, Montero-Escribano P, Pytel V, Porta-Etessam J, et al. ACE2, TMPRSS2, and Furin variants and SARS-CoV-2 infection in Madrid, Spain. Journal of medical virology 2021;93:863-869. [DOI:10.1002/jmv.26319]
35. Klaassen K, Stankovic B, Zukic B, Kotur N, Gasic V, Pavlovic S, et al. Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 2020;84:104498. [DOI:10.1016/j.meegid.2020.104498]
36. van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, et al. Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA 2020;324:663-673. [DOI:10.1001/jama.2020.13719]
37. Fujikura K, Uesaka K. Genetic variations in the human severe acute respiratory syndrome coronavirus receptor ACE2 and serine protease TMPRSS2. Journal of clinical pathology 2020. [DOI:10.1136/jclinpath-2020-206867]
38. Zisman LS. ACE and ACE2: a tale of two enzymes. European Heart Journal 2005;26:322-324. [DOI:10.1093/eurheartj/ehi043]
39. Zhang Y, El-Far M, Dupuy FP, Abdel-Hakeem MS, He Z, Procopio FA, et al. HCV RNA Activates APCs via TLR7/TLR8 While Virus Selectively Stimulates Macrophages Without Inducing Antiviral Responses. Scientific reports 2016;6:29447. [DOI:10.1038/srep29447]
40. Aarabi M, Memariani T, Arefi S, Aarabi M, Hantoosh Zadeh S, Akhondi MA, et al. Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme and coagulation factor XIII genes in patients with recurrent spontaneous abortion. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2011;24:545-548. [DOI:10.3109/14767058.2010.511331]
42. Wang K, Chen W, Zhang Z, Deng Y, Lian JQ, Du P, et al. CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal transduction and targeted therapy 2020;5:283. [DOI:10.1038/s41392-020-00426-x]
43. Bian H, Zheng Z-H, Wei D, Zhang Z, Kang W-Z, Hao C-Q, et al. Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial. medRxiv 2020:2020.2003.2021.20040691. [DOI:10.1101/2020.03.21.20040691]
44. Radzikowska U, Ding M, Tan G, Zhakparov D, Peng Y, Wawrzyniak P, et al. Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID-19 risk factors. Allergy 2020;75:2829-2845. [DOI:10.1111/all.14429]
45. Onofrio L, Caraglia M, Facchini G, Margherita V, Placido S, Buonerba C. Toll-like receptors and COVID-19: a two-faced story with an exciting ending. Future Sci OA 2020;6:Fso605. [DOI:10.2144/fsoa-2020-0091]
46. Onofrio L, Caraglia M, Facchini G, Margherita V, Placido SD, Buonerba C. Toll-like receptors and COVID-19: a two-faced story with an exciting ending. Future Science OA 2020;6:FSO605. [DOI:10.2144/fsoa-2020-0091]
47. Marsh LM, Cakarova L, Kwapiszewska G, von Wulffen W, Herold S, Seeger W, et al. Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair. American journal of physiology Lung cellular and molecular physiology 2009;296:L442-452. [DOI:10.1152/ajplung.00525.2007]
48. Maghsood F, Mirshafiey A, Farahani MM, Modarressi MH, Jafari P, Motevaseli E. Dual Effects of Cell Free Supernatants from Lactobacillus acidophilus and Lactobacillus rhamnosus GG in Regulation of MMP-9 by Up-Regulating TIMP-1 and Down-Regulating CD147 in PMADifferentiated THP-1 Cells. Cell journal 2018;19:559-568.
49. Vargoorani ME, Modarressi MH, Vaziri F, Motevaseli E, Siadat SD. Stimulatory effects of Lactobacillus casei derived extracellular vesicles on toll-like receptor 9 gene expression and cytokine profile in human intestinal epithelial cells. Journal of diabetes and metabolic disorders 2020;19:223-231. [DOI:10.1007/s40200-020-00495-3]
50. Aminaei M, Karami F, Marvibaigi M, Sotoodehnejadnematalahi F, Tajabadi Ebrahimi M. Primary evidence on the potential of Lactobacillus paracasei in treatment of hepatocellular carcinoma. 2018;1:27-29.
Send email to the article author

Add your comments about this article
Your username or Email:


XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Karami F, Modarressi M H. Review on the role of host genetic factors in the susceptibility to SARS-CoV-2. MEDICAL SCIENCES 2022; 32 (4) :337-346
URL: http://tmuj.iautmu.ac.ir/article-1-1989-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 32, Issue 4 (winter 2022) Back to browse issues page
فصلنامه علوم پزشکی دانشگاه آزاد اسلامی واحد پزشکی تهران Medical Science Journal of Islamic Azad Univesity - Tehran Medical Branch
Persian site map - English site map - Created in 0.05 seconds with 37 queries by YEKTAWEB 4645