tetano
Editor, Senior Moderator
Int Immunopharmacol
. 2023 Nov 9;125(Pt B):111155.
doi: 10.1016/j.intimp.2023.111155. Online ahead of print. MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study
Bruna Ramos Tosta[SUP] 1 [/SUP], Ingrid Marins de Almeida[SUP] 1 [/SUP], Laiane da Cruz Pena[SUP] 1 [/SUP], Hatilla Dos Santos Silva[SUP] 1 [/SUP], Fabiane S Reis-Goes[SUP] 2 [/SUP], Nívia N Silva[SUP] 2 [/SUP], João Victor Andrade Cruz[SUP] 1 [/SUP], Mailane Dos Anjos Silva[SUP] 1 [/SUP], Jéssica Francisco de Araújo[SUP] 1 [/SUP], Juliana Lopes Rodrigues[SUP] 1 [/SUP], Gabriella Oliveira[SUP] 3 [/SUP], Ricardo Gassmann Figueiredo[SUP] 4 [/SUP], Sara Nunes Vaz[SUP] 5 [/SUP], Iris Montaño-Castellón[SUP] 5 [/SUP], Daniele Santana[SUP] 5 [/SUP], Fabyan Esberard de Lima Beltrão[SUP] 6 [/SUP], Valdirene Leão Carneiro[SUP] 7 [/SUP], Gubio Soares Campos[SUP] 8 [/SUP], Carlos Brites[SUP] 5 [/SUP], Vitor Fortuna[SUP] 2 [/SUP], Camila Alexandrina Figueiredo[SUP] 1 [/SUP], Soraya Castro Trindade[SUP] 9 [/SUP], Helton Estrela Ramos[SUP] 10 [/SUP], Ryan Dos Santos Costa[SUP] 11 [/SUP]
Affiliations
Background: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response.
Objective: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes.
Methods: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured.
Results: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively.
Conclusions: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.
Keywords: COVID-19; Genetic variants; Severe; mTOR.
. 2023 Nov 9;125(Pt B):111155.
doi: 10.1016/j.intimp.2023.111155. Online ahead of print. MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study
Bruna Ramos Tosta[SUP] 1 [/SUP], Ingrid Marins de Almeida[SUP] 1 [/SUP], Laiane da Cruz Pena[SUP] 1 [/SUP], Hatilla Dos Santos Silva[SUP] 1 [/SUP], Fabiane S Reis-Goes[SUP] 2 [/SUP], Nívia N Silva[SUP] 2 [/SUP], João Victor Andrade Cruz[SUP] 1 [/SUP], Mailane Dos Anjos Silva[SUP] 1 [/SUP], Jéssica Francisco de Araújo[SUP] 1 [/SUP], Juliana Lopes Rodrigues[SUP] 1 [/SUP], Gabriella Oliveira[SUP] 3 [/SUP], Ricardo Gassmann Figueiredo[SUP] 4 [/SUP], Sara Nunes Vaz[SUP] 5 [/SUP], Iris Montaño-Castellón[SUP] 5 [/SUP], Daniele Santana[SUP] 5 [/SUP], Fabyan Esberard de Lima Beltrão[SUP] 6 [/SUP], Valdirene Leão Carneiro[SUP] 7 [/SUP], Gubio Soares Campos[SUP] 8 [/SUP], Carlos Brites[SUP] 5 [/SUP], Vitor Fortuna[SUP] 2 [/SUP], Camila Alexandrina Figueiredo[SUP] 1 [/SUP], Soraya Castro Trindade[SUP] 9 [/SUP], Helton Estrela Ramos[SUP] 10 [/SUP], Ryan Dos Santos Costa[SUP] 11 [/SUP]
Affiliations
- PMID: 37951192
- DOI: 10.1016/j.intimp.2023.111155
Background: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response.
Objective: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes.
Methods: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured.
Results: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively.
Conclusions: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.
Keywords: COVID-19; Genetic variants; Severe; mTOR.