Relação do gene TGF-β1 com o prognóstico de pacientes com Covid-19

Autores

DOI:

https://doi.org/10.33448/rsd-v11i15.36658

Palavras-chave:

Covid-19; Citocinas; Polimorfismo genético; SARS-CoV-2; TGF-β1.

Resumo

Este estudo teve como objetivo investigar o papel do gene TGF-β1 na infecção por SARS-CoV-2. Participaram 178 indivíduos diagnosticados com Covid-19, que foram divididos em dois grupos relacionados ao desfecho (alta ou óbito). A genotipagem dos polimorfismos rs1800468 e rs1800469 do gene TGF-β1 foi realizada em 178 amostras, utilizando a técnica de discriminação alélica e, a análise da expressão gênica foi realizada em 93 amostras por Real Time PCR. Não houve associação entre as frequências genotípicas dos polimorfismos do gene TGF-β1 analisados ​​com o prognóstico de pacientes com Covid-19. Não houve diferença significativa entre a expressão gênica e os dados clínicos avaliados. Foi observada diferença estatisticamente significativa na expressão do gene TGF-β1 entre os genótipos CT e TT do polimorfismo rs1800469, com menor expressão gênica na presença do genótipo TT. Em relação ao polimorfismo rs1800468, não foi observada diferença estatisticamente significativa na expressão do gene TGF-β1 em relação aos genótipos analisados. O presente estudo concluiu que os polimorfismos rs1800468 e rs1800469 do gene TGF-β1 não estão associados ao prognóstico de pacientes com Covid-19 e que o genótipo TT do polimorfismo rs1800469 reduz a expressão do TGF-β1.

Referências

Broekelmann, T. J., Limper, A. H., Colby, T. V., & McDonald, J. A. (1991). Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proceedings of the National Academy of Sciences of the United States of America, 88(15), 6642–6646.

Casanova, J. L., Su, H. C., & COVID Human Genetic Effort (2020). A Global Effort to Define the Human Genetics of Protective Immunity to SARS-CoV-2 Infection. Cell, 181(6), 1194–1199.

Chen, G., Hu, C., Lai, P., Song, Y., Xiu, M., Zhang, H., Zhang, Y., & Huang, P. (2019). Association between TGF-β1 rs1982073/rs1800469 polymorphism and lung cancer susceptibility: An updated meta-analysis involving 7698 cases and controls. Medicine, 98(47).

Costela-Ruiz, V. J., Illescas-Montes, R., Puerta-Puerta, J. M., Ruiz, C., & Melguizo-Rodríguez, L. (2020). SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine & growth factor reviews, 54, 62–75.

de Almeida-Pititto, B., Dualib, P. M., Zajdenverg, L., Dantas, J. R., de Souza, F. D., Rodacki, M., Bertoluci, M. C., & Brazilian Diabetes Society Study Group (SBD) (2020). Severity and mortality of COVID 19 in patients with diabetes, hypertension and cardiovascular disease: a meta-analysis. Diabetology & metabolic syndrome, 12, 75.

Di Maria, E., Latini, A., Borgiani, P., & Novelli, G. (2020). Genetic variants of the human host influencing the coronavirus-associated phenotypes (SARS, MERS and COVID-19): rapid systematic review and field synopsis. Human genomics, 14(1), 30.

Ferreira-Gomes, M., Kruglov, A., Durek, P., Heinrich, F., Tizian, C., Heinz, G. A., … Mashreghi, M. F. (2021). SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself. Nature communications, 12(1), 1961.

Ghazavi, A., Ganji, A., Keshavarzian, N., Rabiemajd, S., & Mosayebi, G. (2021). Cytokine profile and disease severity in patients with COVID-19. Cytokine, 137, 155323.

Gómez, J., Albaiceta, G. M., García-Clemente, M., López-Larrea, C., Amado-Rodríguez, L., Lopez-Alonso, I., Hermida, T., Enriquez, A. I., Herrero, P., Melón, S., Alvarez-Argüelles, M. E., Boga, J. A., Rojo-Alba, S., Cuesta-Llavona, E., Alvarez, V., Lorca, R., & Coto, E. (2020). Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome. Gene, 762, 145102.

Grainger, D. J., Heathcote, K., Chiano, M., Snieder, H., Kemp, P. R., Metcalfe, J. C., Carter, N. D., & Spector, T. D. (1999). Genetic control of the circulating concentration of transforming growth factor type beta1. Human molecular genetics, 8(1), 93–97.

He, B., Xu, C., Yang, B., Landtblom, A. M., Fredrikson, S., & Hillert, J. (1998). Linkage and association analysis of genes encoding cytokines and myelin proteins in multiple sclerosis. Journal of neuroimmunology, 86(1), 13–19.

Juarez, I., Gutierrez, A., Vaquero-Yuste, C., Molanes-López, E. M., López, A., Lasa, I., Gómez, R., & Martin-Villa, J. M. (2021). TGFB1 polymorphisms and TGF-β1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease. Journal of cellular and molecular medicine, 25(2), 774–783.

Karunasagar, Iddya; Karunasagar, Indrani. (2020). Ongoing COVID-19 Global Crisis and Scientific Challenges. Journal of Health and Allied Sciences NU, 10(01), 01–02.

Khadke, S., Ahmed, N., Ahmed, N., Ratts, R., Raju, S., Gallogly, M., de Lima, M., & Sohail, M. R. (2020). Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents. Virology journal,17(1), 154.

Kim, Y. C., & Jeong, B. H. (2020). 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,12(1), 42.

Li, B., Khanna, A., Sharma, V., Singh, T., Suthanthiran, M., & August, P. (1999). TGF-beta1 DNA polymorphisms, protein levels, and blood pressure. Hypertension (Dallas, Tex. : 1979), 33(1 Pt 2), 271–275.

Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Faravelli, F., Greco, M. A., Pyeritz, R. E., Milewicz, D. M., Coucke, P. J., Cameron, D. E., Braverman, A. C., Byers, P. H., De Paepe, A. M., … Dietz, H. C. (2006). Aneurysm syndromes caused by mutations in the TGF-beta receptor. The New England journal of medicine, 355(8), 788–798.

Luedecking, E. K., DeKosky, S. T., Mehdi, H., Ganguli, M., & Kamboh, M. I. (2000). Analysis of genetic polymorphisms in the transforming growth factor-beta1 gene and the risk of Alzheimer's disease. Human genetics,106(5), 565–569.

Montalvo Villalba, M. C., Valdés Ramírez, O., Muné Jiménez, M., Arencibia Garcia, A., Martinez Alfonso, J., González Baéz, G., Roque Arrieta, R., Rosell Simón, D., Alvárez Gainza, D., Sierra Vázquez, B., Resik Aguirre, S., & Guzmán Tirado, M. G. (2020). Interferon gamma, TGF-β1 and RANTES expression in upper airway samples from SARS-CoV-2 infected patients. Clinical immunology (Orlando, Fla.), 220, 108576.

Morikawa, M., Derynck, R., & Miyazono, K. (2016). TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harbor perspectives in biology, 8(5), a021873.

Rai, P., Kumar, B. K., Deekshit, V. K., Karunasagar, I., & Karunasagar, I. (2021). Detection technologies and recent developments in the diagnosis of COVID-19 infection. Applied microbiology and biotechnology,105(2), 441–455.

Schmittgen, T. D., & Livak, K. J. (2008). Analyzing real-time PCR data by the comparative C(T) method. Nature protocols, 3(6), 1101–1108.

Shen, W. X., Luo, R. C., Wang, J. Q., & Chen, Z. S. (2021). Features of Cytokine Storm Identified by Distinguishing Clinical Manifestations in COVID-19. Frontiers in public health, 9, 671788.

Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., & Calvin, D. (1992). Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature, 359(6397), 693–699.

Tian, J., Yuan, X., Xiao, J., Zhong, Q., Yang, C., Liu, B., Cai, Y., Lu, Z., Wang, J., Wang, Y., Liu, S., Cheng, B., Wang, J., Zhang, M., Wang, L., Niu, S., Yao, Z., Deng, X., Zhou, F., Wei, W., … Wang, Z. (2020). Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study.The Lancet. Oncology, 21(7), 893–903.

Wahl, S. M., Wen, J., & Moutsopoulos, N. (2006). TGF-beta: a mobile purveyor of immune privilege. Immunological reviews, 213, 213–227.

Yamada, Y., Miyauchi, A., Takagi, Y., Nakauchi, K., Miki, N., Mizuno, M., & Harada, A. (2000). Association of a polymorphism of the transforming growth factor beta-1 gene with prevalent vertebral fractures in Japanese women. The American journal of medicine, 109(3), 244–247.

Zheng, R., Fu, Z., & Zhao, Z. (2021). Association of Transforming Growth Factor β1 Gene Polymorphisms and Inflammatory Factor Levels with Susceptibility to Sepsis. Genetic testing and molecular biomarkers, 25(3), 187–198.

Downloads

Publicado

08/11/2022

Como Citar

CARMINATI, C. R. .; CARNEIRO, A. C. D. M. .; CUNHA, A. C. C. H. da; PEREIRA, L. Q.; DE VITO, F. B. .; SILVA, M. V. da .; RODRIGUES JÚNIOR, V.; CINTRA, M. T. R. .; GRECCO, R. L. da S. .; TANAKA, S. C. S. V. .; SOUSA, H. M. de . Relação do gene TGF-β1 com o prognóstico de pacientes com Covid-19. Research, Society and Development, [S. l.], v. 11, n. 15, p. e03111536658, 2022. DOI: 10.33448/rsd-v11i15.36658. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/36658. Acesso em: 15 dez. 2024.

Edição

Seção

Ciências da Saúde