Human genes associated with SARS-CoV-2 infection

Authors

Keywords:

SARS-CoV-2, coronavirus infections, Covid-19, genetics, genetic predisposition to disease

Abstract

Background:

The clinical variability of SARS-CoV-2 infection is partially due to genetic factors.

Objective:

To describe the main Covid-19 susceptibility genes.

Methodology:

A literature review was performed in Google Scholar, SciELO, Annual Reviews and PubMed Central. The descriptors used to search the documents were consulted in DeCS: SARS-CoV-2, Covid-19, genetics and genetic predisposition to disease. Full text articles available in English and Spanish were selected, rather from peer-reviewed journals.

Results:

Genes involved in SARS-CoV-2 infection include DDX1 which promotes viral replication, IFITM1, IFITM2, IFITM3, IFNAR2 encoding interferon-induced proteins, receptor genes (ACE2, ANPEP, DPP4), protease genes (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) that contribute to viral entry, immune response genes such as ABO and metallopeptidases such as the ADAM family. Risk genetic polymorphisms have been detected.

Conclusions:

In SARS-CoV-2 infection, there is a complex interaction between environmental and genetic factors that determine the susceptibility of individuals to Covid and its severity. The role of genes in Covid-19 susceptibility should be further investigated.

Downloads

Download data is not yet available.

Author Biography

María Teresa Díaz Armas, Escuela Superior Politécnica de Chimborazo (ESPOCH), Riobamba, Chimborazo

Especialista en Medicina General Integral (MGI). Máster en Asesoramiento Genético.  Escuela Superior Politécnica de Chimborazo. Riobamba, Ecuador. maite.diazarmas@yahoo.com; maite.diaz@yahoo.com

References

1. Conceicao C, Thakur N, Human S, Kelly JT, Logan L, Bialy D, et al. The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins. PLoS Biol [Internet]. 2020 [cited 2021 Nov 06];18(12):[approx.p.27. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751883/pdf/pbio.3001016.pdfç

2. Dobrindt K, Hoagland DA, Seah C, Kassim B, O'Shea CP, Murphy A, et al. Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem Cell Reports [Internet]. 2021 [cited 2021 Nov 06];16(3): 505-518. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881728/pdf/main.pdf

3. López-Farré A. Los genes de la susceptibilidad a la infección por Covid-19. An RANM [Internet]. 2020 [citado 17 Dic 2021];137(02):117-120. Disponible en: https://analesranm.es/wp-content/uploads/2020/numero_137_02/pdfs/rev04.pdf

4. Morales Peralta E, Alvarez Fornaris MA. Covid-19: aspectos relacionados a la susceptibilidad genética y defectos congénitos. Rev haban cienc méd [Internet]. 2020 [citado 17 Dic 2021];19(5):[approx.12p.]. Disponible en: http://scielo.sld.cu/pdf/rhcm/v19n5/1729-519X-rhcm-19-05-e3595.pdf

5. Daniloski Z, Jordan TX, Wessels HH, Hoagland DA, Kasela S, Legut M, et al. Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells. Cell [Internet]. 2021 [cited 2021 Dec 17];184(1):92-105.e16. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584921/pdf/main.pdf

6. Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends Immunol. 2020 [cited 17 Dec 2021];41(12):1100-1115. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556779/pdf/main.pdf

7. Gill D, Arvanitis M, Carter P, Hernández Cordero AI, Jo B, et al. ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study. R Soc Open Sci [Internet]. 2020 [cited 2021 Dec 17]:7(11). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735342/pdf/rsos200958.pdf

8. Fallerini C, Picchiotti N, Baldassarri M, Zguro K, Daga S, Fava F, et al. Common, low-frequency, rare, and ultra-rare coding variants contribute to Covid-19 severity. Hum Genet [Internet]. 2021 [cited 2021 Dec 17];141(1):147-173. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661833/pdf/439_2021_Article_2397.pdf

9. Kasela S, Ortega VE, Martorella M, Garudadri S, Nguyen J, Ampleford E, et al. Genetic and non-genetic factors affecting the expression of Covid-19-relevant genes in the large airway epithelium. Genome Med [Internet]. 2021 [cited 2021 Nov 06];13(1):[approx.17p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059115/pdf/13073_2021_Article_866.pdf

10. Kucher AN, Babushkina NP, Sleptcov AA, Nazarenko MS. Genetic Control of Human Infection with SARS-CoV-2. Russ J Genet [Internet]. 2021 [cited 2021 Dec 17];7(6):627-641. Available from: https://link.springer.com/article/10.1134/S1022795421050057

11. Jahanafrooz Z, Chen Z, Bao J, Li H, Lipworth L, Guo X. An overview of human proteins and genes involved in SARS-CoV-2 infection. Gene [Internet]. 2021 [cited 2021 Dec 06];808:145963. Available from: https://doi.org/10.1016/j.gene.2021.145963

12. Zhang Q, Xiang R, Huo S, Zhou Y, Jiang S, Wang Q, et al. Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Signal Transduct Target Ther [Internet]. 2021 [cited 2021 Dec 17];6:233. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193598/pdf/41392_2021_Article_653.pdf

13. Rodríguez Duque R, Miguel Soca PE. Farmacogenómica: principios y aplicaciones en la práctica médica. Rev haban cienc méd [Internet]. 2020 [citado 06 Nov 2021];19(6):e3128. Disponible en: http://scielo.sld.cu/pdf/rhcm/v19n6/1729-519X-rhcm-19-06-e3128.pdf

14. Sánchez-Artigas R, Díaz-Armas M, Rodríguez-Duque R, Miguel-Soca P. Principios y aplicaciones médicas de la edición de genes mediante CRISPR/Cas. Medisur [Internet]. 2021 [citado 06 Nov 2021];19(6):[aprox. 9 p.]. Disponible en: http://www.medisur.sld.cu/index.php/medisur/article/view/5279/3643

15. Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, et al. Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for Covid-19. Nat Med [Internet]. 2021 [cited 2021 Dec 17];27(4):668-676. Available from: https://www.nature.com/articles/s41591-021-01310-z.pdf

16. Pathak GA, Singh K, Miller-Fleming TW, Wendt FR, Ehsan N, Hou K, et al. Integrative genomic analyses identify susceptibility genes underlying Covid-19 hospitalization. Nat Commun [Internet]. 2021 [cited 2021 Dec 17] ;12(1):[approx. 11p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316582/pdf/41467_2021_Article_24824.pdf

17. Liu D, Yang J, Feng B, Lue W, Zhao C, Li L. Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of Covid-19. J Infect [Internet]. 2021 [cited 2021 Nov 06];82(1):126-132. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698677/pdf/main.pdf

18. Raskin S. Genetics of Covid-19. J Ped [Internet]. 2021 [cited 2021 Nov 06];97(4):378-386. Available from: https://jped.elsevier.es/en-pdf-S0021755720302114

19. Kadam SB, Sukhramani GS, Bishnoi P, Pable AA, Barvkar VT. SARS‐CoV‐2, the pandemic coronavirus: Molecular and structural insights. J Basic Microbiol [Internet]. 2021 [cited 2021 Dec 17];61(3):180-202. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013332/pdf/JOBM-61-180.pdf

20. Desimmie BA, Raru YY, Awadh HM, He P, Teka S, Willenburg KS. Insights intoSARS-CoV-2 Persistence and Its Relevance. Viruses [Internet]. 2021 [cited 2021 Nov 6];13(6):[approx.22p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013332/pdf/JOBM-61-180.pdf

21. Amanat F, Thapa M, Lei T, Ahmed SMS, Adelsberg DC, Carreño JM, et al. SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2. Cell [Internet]. 2021 [cited 2021 Nov 06];184(15): 3936-3948. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185186/pdf/main.pdf

22. Expósito-Lara A, Feria-Díaz G, González-Benítez S, Miguel-Soca P. Variantes genéticas del SARS-CoV-2 y sus implicaciones clínicas. Medisan [Internet]. 2021 [citado 17 Dic 2021];25(6). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185186/pdf/main.pdf

23. Pacheco-Romero J. El enigma del coronavirus – Nueva variante ómicron – Nuevas inquietudes - La mujer. Rev peru ginecol obstet [Internet]. 2021 [citado 06 Dic 2021];67(4). Disponible en: http://51.222.106.123/index.php/RPGO/article/view/2380/2550

24. Zhu C, He G, Yin Q, Zeng L, Ye X, Shi Y, et al. Molecular biology of the SARs‐CoV‐2 spike protein: A review of current knowledge. J Med Virol [Internet]. 2021 [cited 2021 Dec 17];93(10):5729-5741. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.27132

25. Díaz-Armas M, Sánchez-Artigas R, Matute-Respo T, Llumiquinga-Achi R. Proteína de la espícula del virus SARS-CoV-2 y su relación con la enzima convertidora de angiotensina-2. RIC [Internet]. 2021 [citado 06 Dic 2021];100 (5). Disponible en: http://www.revinfcientifica.sld.cu/index.php/ric/article/view/3633/4918

26. Yeung ML, Teng JLL, Jia L, Zhang C, Huang C, Cai J-P, et al. Soluble ACE2-mediated cell entry ofSARS-CoV-2 via interaction with proteinsrelated to the renin-angiotensin system. Cell [Internet]. 2021 [cited 2021 Dec 06];184(8): 2212-2228. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923941/pdf/main.pdf

27. Baranova A, Cao H, Zhang F. Unraveling Risk Genes of Covid-19 by Multi-Omics Integrative Analyses. Front Med (Lausanne) [Internet]. 2021 [cited 2021 Dec 17];8:[approx.8p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452849/pdf/fmed-08-738687.pdf

28. Liu Y, Hu G, Wang Y, Ren W, Zhao X, Ji F, et al. Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2. Proc Natl Acad Sci U S A [Internet]. 2021 [cited 2021 Dec 17]; 118(12):[approx.9p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000431/pdf/pnas.202025373.pdf

29. Secolin R, de Araujo TK, Gonsales MC, Rocha CS, Naslavsky M, Marco L, et al. Genetic variability in Covid-19-related genes in the Brazilian population. Hum Genome Var [Internet]. 2021 [cited 2021 Dec 17];8:[approx.9p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017521/pdf/41439_2021_Article_146.pdf

30. Winstone H, Lista MJ, Reid AC, BoutonC, Pickering S, Galao RP, et al. The polybasiccleavage site in SARS-CoV-2 spike modulatesviral sensitivity to type I interferon and IFITM2. J Virol [Internet]. 2021 [cited 2021 Dec 06];95(9):e02422-20. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104117/pdf/JVI.02422-20.pdf

31. Vanderheiden A, Ralfs P, Chirkova T, Upadhyay AA, Zimmerman MG, Bedoya S, et al. Type I and Type III Interferons Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures. J Virol [Internet]. 2020 [cited 2021 Dec 17];94(19):e00985-20. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495371/pdf/JVI.00985-20.pdfç

32. Carapito R, Li R, Helms J, Carapito C, Gujja S, Rolli V, et al. Identification of driver genes for critical forms of Covid-19 in a deeply phenotyped young patient cohort. Sci Transl Med. 2021[cited 2021 Dec 06]; 10:1126. Available from: https://www.science.org/doi/pdf/10.1126/scitranslmed.abj7521

33. Aljohmani A, Yildiz D. A Disintegrin and Metalloproteinase—Control Elements in Infectious Diseases. Front Cardiovasc Med [Internet]. 2020 [cited 2021 Dec 06];7: [approx.14p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772189/pdf/fcvm-07-608281.pdf

34. Covid-19 Host Genetics Initiative. Mapping the human genetic architecture of Covid-19. Nature [Internet]. 2021 [cited 2021 Dec 06];600(7889):472-477. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674144/pdf/41586_2021_Article_3767.pdf

35. Almaguer-Mederos L, Cuello-Almarales D, Almaguer-Gotay D. Rol de los genes ACE2 y TMPRSS2 en la susceptibilidad o gravedad de la Covid-19. Anales de la Academia de Ciencias de Cuba [Internet]. 2020 [citado 06 Dic 2021];10(2). Disponible en: http://www.revistaccuba.cu/index.php/revacc/article/view/799/861

36. van Blokland IV, Lanting P, Ori APS, Vonk JM, Warmerdam RCA, Herkert JC, et al. Using symptom-based case predictions to identify host genetic factors that contribute to Covid-19 susceptibility. PLoS One [Internet]. 2021 [cited 2021 Dec 06];16(8):[approx.14p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357137/pdf/pone.0255402.pdf

37. Andolfo I, Russo R, Lasorsa VA, Cantalupo S, Rosato BE, Bonfiglio F, et al. Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe Covid-19. Science [Internet]. 2021 [cited 2021 Dec 06];24(4). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968217/pdf/main.pdf

38. Medina-Espitia ÓL, Mendoza-Beltrán F, Anaya-Almanza AM, Molano-Salazar ÓA. Covid-19 y metabolismo: una mirada más allá del sistema respiratorio y de la enfermedad trombótica. Rev Colomb Cardiol [Internet]. 2021 [citado 06/12/2021]; 28(4): 366-373. Disponible en: http://www.scielo.org.co/pdf/rcca/v28n4/0120-5633-rcca-28-4-366.pdf

39. Bermúdez-Garcell A, Serrano-Gámez N, Teruel-Ginés R, Sánchez-Sánchez R, Sigcho-Romero C. Mecanismos básicos de la epigenética. CCM [Internet]. 2020 [citado 06 Dic 2021];24(1). Disponible en: http://www.revcocmed.sld.cu/index.php/cocmed/article/view/3448/1516

40. Al-Benna S. Association of high level gene expression of ACE2 in adipose tissue with mortality of Covid-19 infection in obese patients. Obes Med [Internet]. 2020 [cited 2021 Dec 17];9:[approx.5p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368415/pdf/main.pdf

41. Polverino F, Kheradmand F. Covid-19, COPD, and AECOPD: Immunological, Epidemiological, and Clinical Aspects. Front Med [Internet]. 2021 [cited 2021 Dec 17];7:[approx.8p.]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847987/pdf/fmed-07-627278.pdf

Published

2022-03-08

How to Cite

1.
Rodríguez Duque R, Rodríguez Moldón Y, Díaz Armas MT. Human genes associated with SARS-CoV-2 infection. Gac méd espirit [Internet]. 2022 Mar. 8 [cited 2025 Oct. 19];24(1). Available from: https://revgmespirituana.sld.cu/index.php/gme/article/view/2370

Issue

Section

BIBLIOGRAPHIC REVIEW