Single nucleotide polymorphisms located in <i>TNFA, IL1RN, IL6R</i>, and <i>IL6</i> genes are associated with COVID‐19 risk and severity in an Iranian population

Rokni, Mohsen; Sarhadi, Mohammad; Nia, Milad Heidari; Khosroshahi, Leila Mohamed; Asghari, Somaye; Sargazi, Saman; Mirinejad, Shekoufeh

doi:10.1002/cbin.11807

“…In this respect, Nia et al showed that TNF α /TNF β polymorphisms might substantially affect COVID-19 susceptibility [ 43 ]. In a case-control study, Rokni et al reported that carrying the A allele in TNFA-rs361525, the C allele in IL1RN-rs419598, and the A allele in IL6R-rs2228145 was related to susceptibility to developing COVID-19 [ 44 ]. These findings indicate that SNPs in several other candidate genes involved in the inflammatory response might also impact susceptibility to COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

Sá

¹

,

Neira-Goulart

²

,

Ribeiro-Alves

³

et al. 2022

BioMed Research International

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COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease ( WHO < 6 ; n = 76 ), and group 2 included patients with severe/critical COVID-19 ( WHO ≥ 6 ; n = 357 ). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic – National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype ( OR adj = 0.36 ; P = 0.032 ), allele A ( OR adj = 0.93 ; P = 0.010 ), or carrier-A ( OR adj = 0.45 ; P = 0.027 ) in the NLRP3 rs1539019 polymorphism; A/T genotype ( OR adj = 0.5 ; P = 0.045 ), allele T ( OR adj = 0.93 ; P = 0.018 ), or carrier-T ( OR adj = 0.48 ; P = 0.029 ) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C ( OR adj = 0.11 ; P = 0.018 ), A-C-G-C-G ( OR adj = 0.23 ; P = 0.003 ), C-C-G-C-C ( OR adj = 0.37 ; P = 0.021 ), and C-T-G-A-C ( OR adj = 0.04 ; P = 0.0473 ) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

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“…The G/G genotype is suggestive of IL-6 gene overexpression. There were significant differences between the two groups (COVID-19 71% vs. 33% healthy) (95% CI, p < 0.005); conversely, the G/C seemed to exert a more protective activity (53% vs. 24%; 95% CI, p < 0.05) [ 33 , 34 , 35 ]. ( K ) The IL10 (rs1800896) gene polymorphism that compromises the expression of IL10 is implicated in susceptibility to pulmonary infection and general inflammatory states, typical of tuberculosis (PTBC) and ARDS, specifically in adult and elderly.…”

Section: Figurementioning

confidence: 99%

“…Though little is known regarding IL-6 polymorphisms and the pathogenesis of idiopathic pulmonary fibrosis in SARS-CoV-2 infections, data tend to confirm that the IL-6 174 is associated with elevated inflammatory patterns in the outcome of SARS-CoV-2 pneumonia. This event could be explained by the direct impact on CD4 and CD8 T cell fate exerted by IL-6 174 [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection

Balzanelli

¹

,

Distratis

²

,

Lazzaro

³

et al. 2022

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Many factors may influence the risk of being infected by SARS-CoV-2, the coronavirus responsible for coronavirus disease 2019 (COVID-19). Exposure to the virus cannot explain the variety of an individual’s responses to the virus and the high differences of effect that the virus may cause to some. While a person’s preexisting condition and their immune defenses have been confirmed to play a major role in the disease progression, there is still much to learn about hosts’ genetic makeup towards COVID-19 susceptibility and risk. The host genetic makeup may have direct influence on the grade of predisposition and outcomes of COVID-19. In this study, we aimed to investigate the presence of relevant genetic single nucleotide polymorphisms (SNPs), the peripheral blood level of IL6, vitamin D and arterial blood gas (ABG) markers (pH, oxygen-SpO2 and carbon dioxide-SpCO2) on two groups, COVID-19 (n = 41, study), and the healthy (n = 43, control). We analyzed cytokine and interleukin genes in charge of both pro-inflammatory and immune-modulating responses and those genes that are considered involved in the COVID-19 progression and complications. Thus, we selected major genes, such as IL1β, IL1RN (IL-1 β and α receptor) IL6, IL6R (IL-6 receptor), IL10, IFNγ (interferon gamma), TNFα (tumor necrosis factor alpha), ACE2 (angiotensin converting enzyme), SERPINA3 (Alpha-1-Antiproteinase, Antitrypsin member of Serpin 3 family), VDR (vitamin D receptor Tak1, Bsm1 and Fok1), and CRP (c-reactive protein). Though more research is needed, these findings may give a better representation of virus pleiotropic activity and its relation to the immune system.

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“…The coronavirus disease 2019 (COVID- 19) was professed an international public health emergency in January 2020 by the World Health Organization, after a short period of time it arose in Wuhan, China, in late 2019. 1 On March 11, 2020, the new severe acute respiratory syndrome coronavirus outbreak was officially designated as a pandemic.…”

Section: Introductionmentioning

confidence: 99%

“…(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) Journal of Pediatric Infectious Diseases Vol 18. No.…”

mentioning

confidence: 99%

Association of Tumor Necrosis Factor-Alpha (TNF-α) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

Uysalol

¹

,

Serin

²

,

Oyacı

³

et al. 2022

J Pediatr Infect Dis

1

0

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Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-α (TNF-α) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA > Del) and TNF-α (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19). Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups. Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p < 0.05). The GG genotype of the TNF-α was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-α was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold). Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes.

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Single nucleotide polymorphisms located in TNFA, IL1RN, IL6R, and IL6 genes are associated with COVID‐19 risk and severity in an Iranian population

Cited by 25 publications

References 83 publications

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil

Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection

Association of Tumor Necrosis Factor-Alpha (TNF-α) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

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