Genes humanos asociados a la infección por el SARS-CoV-2

Raisa Rodríguez Duque, Yarimi Rodríguez Moldón, María Teresa Díaz Armas

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Resumen

Fundamento: La variabilidad clínica de la infección por el SARS-CoV-2 se debe, en parte, a factores genéticos.

Objetivo: Describir los principales genes de susceptibilidad a la Covid-19.

Metodología: Se realizó una revisión bibliográfica en Google Académico, SciELO, Annual Reviews y PubMed Central. Los descriptores que se utilizaron para la búsqueda de los documentos fueron consultados en el DeCS, estos fueron: SARS-CoV-2, Covid-19, genética y predisposición genética a la enfermedad. Se seleccionaron artículos disponibles a texto completo en inglés y en español, preferentemente de revistas arbitradas por pares.

Resultados: Entre los genes implicados en la infección por el SARS-CoV-2 se encuentran DDX1 que promueve la replicación viral, IFITM1, IFITM2, IFITM3, IFNAR2 que codifican proteínas inducidas por el interferón, los genes de receptores (ACE2, ANPEP, DPP4), los genes de proteasas (TMPRSS2, furin, TMPRSS11D, CTSL, CTSB) que contribuyen a la entrada viral, genes de la respuesta inmune como ABO y metalopeptidasas como la familia ADAM. Se han detectado polimorfismos genéticos de riesgo.

Conclusiones: En la infección por el SARS-CoV-2 se produce una compleja interrelación entre factores ambientales y genéticos que determinan la susceptibilidad de las personas a la Covid y su gravedad. El papel de los genes en la susceptibilidad a la Covid-19 deberá continuar investigándose.

Palabras clave

SARS-CoV-2; COVID-19; genética; predisposición genética a la enfermedad.

Referencias

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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



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