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Observational Study
. 2024 Oct 8:15:1422349.
doi: 10.3389/fimmu.2024.1422349. eCollection 2024.

Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study

Ingrid Marins de Almeida  1 , Bruna Ramos Tosta  1 , Laiane da Cruz Pena  1 , Hatilla Dos Santos Silva  1 , Fabiane S Reis-Goes  2 , Nívia N Silva  2 , João Victor Andrade Cruz  1 , Mailane Dos Anjos Silva  1 , Jéssica Francisco de Araújo  1 , Juliana Lopes Rodrigues  1 , Gabriella Oliveira  3 , Ricardo Gassmann Figueiredo  4 , Sara Nunes Vaz  5 , Iris Montaño-Castellón  5 , Daniele Santana  5 , Alex Torres  2 , Fabyan Esberard de Lima Beltrão  6 , Valdirene Leão Carneiro  7 , Gubio Soares Campos  8 , Carlos Brites  5 , Vitor Fortuna  2 , Camila Alexandrina Figueiredo  1 , Soraya Castro Trindade  2   4 , Helton Estrela Ramos  9 , Ryan Dos Santos Costa  1
Affiliations
Observational Study

Genetic signatures of AKT1 variants associated with worse COVID-19 outcomes - a multicentric observational study

Ingrid Marins de Almeida et al. Front Immunol. .

Abstract

Introduction: The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the AKT1 gene associated with severe COVID-19 outcomes.

Methods: Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the AKT1 variants.

Results: The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease.

Discussion: Our findings contribute to understanding the influence of the AKT1 gene variants on the immunological damage in individuals infected with SARS-CoV-2.

Keywords: AKT1; COVID-19; immunogenetics; polymorphism; severity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Genotypic association of the rs2494746 and rs1130214 variants with cytokine levels. (A) There was no statistical significance in the plasma levels of TNF between the genotypes of the rs2494746; (B) The risk allele C (rs1130214) was significantly associated with increased levels of TNF. Data are presented as median and interquartile ranges for non-parametric distribution. The unpaired two-tailed Mann-Whitney U test was used for comparisons between groups (p= 0.0063).
Figure 2
Figure 2
Genotypic association of the rs2494746 and rs1130214 variants with d-dimer levels in the plasma of individuals with COVID-19 in severe cases of Paraíba. There was no statistical difference between the rs2494746 genotypes in (A) individuals admitted to the ICU and (C) individuals who died. Homozygotes for the C risk allele (rs1130214) were significantly associated with increased d-dimer levels compared to individuals carrying the AC or AA genotype in (B) individuals admitted to the ICU and (D) individuals who died. Data are presented as median and interquartile ranges for non-parametric distribution. The unpaired two-tailed Mann-Whitney U test was used for comparisons between groups (p<0.0001 – p=0.0003).
Figure 3
Figure 3
Kaplan–Meier survival curves of severe COVID-19 patients for genotype of rs2494746 and rs1130214 AKT1 variants. The recessive models showed no statistically significant difference between individuals with at least one C allele compared to homozygote individuals in the rs2494746 variant (A) or the rs1130214 (B).
See this image and copyright information in PMC

References

    1. Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-coV-2 and COVID-19. Nat Rev Microbiol. (2021) 19:141–54. doi: 10.1038/s41579-020-00459-7 - DOI - PMC - PubMed
    1. Darif D, Hammi I, Kihel A, El Idrissi Saik I, Guessous F, Akarid K. The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong? Microb Pathog. (2021) 153:104799. doi: 10.1016/j.micpath.2021.104799 - DOI - PMC - PubMed
    1. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. . Factors associated with COVID-19-related death using OpenSAFELY. Nature. (2020) 584:430–6. doi: 10.1038/s41586-020-2521-4 - DOI - PMC - PubMed
    1. Ersahin T, Tuncbag N, Cetin-Atalay R. The PI3K/AKT/mTOR interactive pathway. Mol Biosyst. (2015) 11:1946–54. doi: 10.1039/C5MB00101C - DOI - PubMed
    1. Appelberg S, Gupta S, Svensson Akusjärvi S, Ambikan AT, Mikaeloff F, Saccon E, et al. . Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells. Emerg Microbes Infect. (2020) 9:1748–60. doi: 10.1080/22221751.2020.1799723 - DOI - PMC - PubMed

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