<i>TNFRSF1B</i> and <i>TNF</i> Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19

Fricke-Galindo, Ingrid; Buendía-Roldán, Ivette; Ruíz, Andy; Palacios, Yadira; Pérez-Rubio, Gloría; Hernández-Zenteno, Rafael de Jesús; Reyes-Melendres, Felipe; Zazueta-Márquez, Armando; Alarcón-Dionet, Aimé; Guzmán-Vargas, Javier; Bravo-Gutiérrez, Omar Andrés; Quintero-Puerta, Teresa; Gutiérrez-Pérez, Ilse Adriana; Nava-Quiroz, Karol J.; Bañuelos-Flores, José Luis; Mejía, Mayra; Rojas-Serrano, Jorge; Ramos-Martı́nez, Espiridión; Guzmán‐Guzmán, Iris Paola; Chávez‐Galán, Leslie; Falfán-Valencia, Ramcés

doi:10.1093/infdis/jiac101

Cited by 13 publications

(17 citation statements)

References 36 publications

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“…24 Galindo et al also studied TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), TNFRSF1B (rs1061622 and rs3397) polymorphisms and they reported that TNF and TNFRSFB1 gene polymorphisms affect the plasma levels of soluble TNFR1 and TNFR2, which are implicated in COVID-19 severity. 29 TNF- inhibitors may be an effective therapy for preventing disease progression in severe SARS-CoV-2 infection, and therefore, determining associations between TNF gene polymorphisms and disease severity will be helpful for the selection of candidates who may benefit from anti-TNF therapy.…”

Section: Discussionmentioning

confidence: 99%

“…However, in studies investigating relationships between genetic variations and the clinical course of COVID-19, only certain genes and certain sequences have been investigated [18][19][20] and there are inconsistencies between the results of these studies. [25][26][27][28][29] Moreover, there are a few Turkish studies on previously published gene polymorphisms that have assessed relationships between COVID-19 and genetic factors. 26,30,31 So hopefully, this study will increase evidence regarding the relationships between gene variants and disease severity, by adding novel variants through the sequencing of three primary genes associated with COVID-19, namely ACE, IFNG, and TNF-a.…”

Section: Introductionmentioning

confidence: 99%

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The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection

Esen

Çeltikçi

Ozer

et al. 2023

Journal of Investigative Medicine

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To investigate the effect of genetic variations in the angiotensin converting enzyme (ACE), interferon (IFNG) and tumor necrosis factor (TNF-α) genes on the severity of coronavirus disease (COVID-19). Between September and December 2021, 33 patients with COVID-19 were included in this prospective study. The patients were classified and compared according to disease severity: mild&moderate (n = 26) vs severe&critical (n = 7). These groups were evaluated to assess possible relationships with ACE, TNF-α and IFNG gene variations using univariate and multivariable analyses. The median age of the mild&moderate group was 45.5 (22–73), and that of the severe&critical group was 58 (49–80) years (p = 0.014). Seventeen (65.4%) of the mild&moderate patients and 3 (42.9%) of severe&critical patients were female (p = 0.393). According to results of univariate analysis, the percentage of patients with the c.418-70C>G variant of the ACE gene was significantly higher in the mild&moderate group (p = 0.027). The ACE gene polymorphisms, c.2312C>T, c.3490G>A, c.3801C>T, and c.731A>G, were each only seen in separate patients with critical disease. The following variants were observed more frequently in the mild&moderate group: c.582C>T, c.3836G>A, c.511+66A>G, c.1488-58T>C, c.3281+25C>T, c.1710-90G>C, c.2193A> G, c.3387T>C for ACE; c.115-3delT for IFNG; and c.27C>T for TNF. It can be expected that patients carrying the ACE gene c.418-70C>G variant may present with a mild clinical manifestation of COVID-19. Several genetic polymorphisms may be associated with pathophysiology, as they appear to help predict COVID-19 severity and enable early identification of the patients requiring aggressive treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection

Esen

Çeltikçi

Ozer

et al. 2023

Journal of Investigative Medicine

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“…In COVID-19 patients, elevated levels of TNF-R1 and TNF-R2 have been detected. 28 In addition, levels of soluble TNF-R1 were correlated with the severity of the disease. 29 Like microbial infections, other xenobiotics could also be detrimental to the health.…”

Section: Discussionmentioning

confidence: 99%

Computational study unravels inhibitory potential of epicatechin gallate against inflammatory and pyroptosis‐associated mediators in COVID‐19

Rajak

Ganguly

2023

MedComm – Future Medicine

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Coronavirus disease‐19 (COVID‐19) is the global health emergency caused by SARS‐CoV‐2. Upon infection, antigenic determinants of the virus trigger massive production of proinflammatory/pyroptosis‐associated proteins, resulting in cytokine storm, tissue damage, and multiorgan failure. Therefore, these proinflammatory/pyroptosis‐associated mediators are promising therapeutic targets to combat COVID‐19. Epicatechin gallate (ECG) is a polyphenol found in green tea. It has antioxidative and anti‐inflammatory properties. Hence, in the present study, ECG was selected to explore its binding potential for inflammatory mediators such as interleukins, interferon‐γ (IFNγ), and tumor necrosis factor‐α (TNF‐α), along with their native receptors. In addition, the interacting potential of ECG with pyroptosis‐associated proteins, viz. caspases and BAX has also been investigated. Molecular docking analysis has revealed that ECG interacts with interleukins, IFNγ, TNF‐α, cytokine receptors, caspase‐1/4/11, and BAX with significant binding affinity. Several amino acid residues of these mediators were blocked by ECG through stable hydrogen bonds and hydrophobic contacts. ECG interacted with caspase‐11, BAX, and TNF‐R1 with better binding affinities. Therefore, the present in silico study indicates that ECG could be a potential drug to subvert cytokine storm and pyroptosis during COVID‐19.

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“…Furthermore, the TNF rs909253 allele has been significantly more common in COVID‐19 patients than in the control population 53 . In a recent study, TNFRSF1B rs3397 or TT genotype was associated with lower Horowitz index (PaO 2 /FiO 2 ratio) compared to CT + CC genotypes being related to different TNFR1 and TNFR2 levels 54 …”

Section: Tnf Gene Polymorphismsmentioning

confidence: 98%

“… 53 In a recent study, TNFRSF1B rs3397 or TT genotype was associated with lower Horowitz index (PaO 2 /FiO 2 ratio) compared to CT + CC genotypes being related to different TNFR1 and TNFR2 levels. 54 …”

Section: Tnf Gene Polymorphismsmentioning

confidence: 99%

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

Vakil

Mansoori

Al-Awsi

et al. 2022

Journal of Medical Virology

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Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease-19 (COVID-19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID-19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID-19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll-like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID-19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID-19 disease severity. Understanding host immune gene variations associated with the SARS-COV-2 infection opens insights to control the pathophysiology of emerging viral infections.

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TNFRSF1B and TNF Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19

Cited by 13 publications

References 36 publications

The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection

The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection

Computational study unravels inhibitory potential of epicatechin gallate against inflammatory and pyroptosis‐associated mediators in COVID‐19

Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

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