Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil

<b>Background/Objectives:</b> Genetic variants in cytokine genes such as <i>IL1B</i>, <i>IL6</i>, and <i>TNF</i> may influence inflammatory responses to SARS-CoV-2 and affect disease severity. This study investigates the role of these variants in relat...

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Main Authors: Mariléa Furtado Feira, Renan Cesar Sbruzzi, Miriãn Ferrão Maciel-Fiuza, Vitória Carolina Griebeler, Tatiana Schaffer Gregianini, Letícia Garay Martins, Nathan Araujo Cadore, Jose Artur Bogo Chies, Thayne Woycinck Kowalski, Fernanda Sales Luiz Vianna
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Language:English
Published: MDPI AG 2025-05-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/15/11/1403
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author Mariléa Furtado Feira
Renan Cesar Sbruzzi
Miriãn Ferrão Maciel-Fiuza
Vitória Carolina Griebeler
Tatiana Schaffer Gregianini
Letícia Garay Martins
Nathan Araujo Cadore
Jose Artur Bogo Chies
Thayne Woycinck Kowalski
Fernanda Sales Luiz Vianna
author_facet Mariléa Furtado Feira
Renan Cesar Sbruzzi
Miriãn Ferrão Maciel-Fiuza
Vitória Carolina Griebeler
Tatiana Schaffer Gregianini
Letícia Garay Martins
Nathan Araujo Cadore
Jose Artur Bogo Chies
Thayne Woycinck Kowalski
Fernanda Sales Luiz Vianna
author_sort Mariléa Furtado Feira
collection DOAJ
description <b>Background/Objectives:</b> Genetic variants in cytokine genes such as <i>IL1B</i>, <i>IL6</i>, and <i>TNF</i> may influence inflammatory responses to SARS-CoV-2 and affect disease severity. This study investigates the role of these variants in relation to COVID-19 outcomes, including hospitalization, ICU admission, and mortality. <b>Methods:</b> A total of 500 unvaccinated individuals from southern Brazil diagnosed with COVID-19 via RT-PCR were analyzed. DNA was extracted from nasopharyngeal swabs and genotyped for functional variants selected based on evidence of regulatory function and prior associations with inflammatory outcomes—<i>IL1B</i> (rs4848306, rs1143623, rs16944, rs1143627), <i>IL6</i> (rs1800795, rs2069832, rs2069840, rs2069845), and <i>TNF</i> (rs1799964, rs1800630, rs1799724, rs1800629, rs361525). Multivariate logistic regression analysis, adjusted for sex and age, was employed to assess the association between these genetic variants and severe clinical outcomes. <b>Results:</b> The results indicated that the <i>IL1B</i> rs16944-AG (OR: 1.98 [95% CI: 1.22–3.23], <i>p</i> = 0.006) and <i>TNF</i> rs1799964-CT (OR: 1.97 [95% CI: 1.22–3.22], <i>p</i> = 0.006) genotypes were associated with the need for hospitalization, while TNF rs1800630-AA (OR: 2.37 [95% CI: 1.08–5.33], <i>p</i> = 0.034) was associated with ICU admission. Additionally, the CC genotype of <i>TNF</i> rs1799964 was associated with a higher risk of mortality (OR: 3.73 [95% CI: 1.21–14.37], <i>p</i> = 0.034). <b>Conclusions:</b> Genetic variants—specifically <i>IL1B</i> rs16944 and rs1143627, and <i>TNF</i> rs1799964 and rs1800630—were associated with COVID-19 severity and should be further investigated in larger studies to evaluate their potential as predictive markers of severe outcomes in COVID-19.
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spelling doaj-art-af96cdec4a9240ae907f1ad9697a7c5d2025-08-20T02:33:01ZengMDPI AGDiagnostics2075-44182025-05-011511140310.3390/diagnostics15111403Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern BrazilMariléa Furtado Feira0Renan Cesar Sbruzzi1Miriãn Ferrão Maciel-Fiuza2Vitória Carolina Griebeler3Tatiana Schaffer Gregianini4Letícia Garay Martins5Nathan Araujo Cadore6Jose Artur Bogo Chies7Thayne Woycinck Kowalski8Fernanda Sales Luiz Vianna9Postgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilPostgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilPostgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilLaboratory of Genomic Medicine, Center of Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre 90035-903, RS, BrazilLaboratório Central do Centro Estadual de Vigilância em Saúde da do Rio Grande do Sul (LACEN), Secretaria da Saúde do estado do Rio Grande do Sul (LACEN/CEVS/SES-RS), Porto Alegre 90620-000, RS, BrazilCentro Estadual de Vigilância em Saúde da Secretaria de Saúde do estado do Rio Grande do Sul (CEVS/SES-RS), Porto Alegre 90620-000, RS, BrazilPostgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilPostgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilPostgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, BrazilPostgraduate Program in Genetics and Molecular Biology (PPGBM), Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, Brazil<b>Background/Objectives:</b> Genetic variants in cytokine genes such as <i>IL1B</i>, <i>IL6</i>, and <i>TNF</i> may influence inflammatory responses to SARS-CoV-2 and affect disease severity. This study investigates the role of these variants in relation to COVID-19 outcomes, including hospitalization, ICU admission, and mortality. <b>Methods:</b> A total of 500 unvaccinated individuals from southern Brazil diagnosed with COVID-19 via RT-PCR were analyzed. DNA was extracted from nasopharyngeal swabs and genotyped for functional variants selected based on evidence of regulatory function and prior associations with inflammatory outcomes—<i>IL1B</i> (rs4848306, rs1143623, rs16944, rs1143627), <i>IL6</i> (rs1800795, rs2069832, rs2069840, rs2069845), and <i>TNF</i> (rs1799964, rs1800630, rs1799724, rs1800629, rs361525). Multivariate logistic regression analysis, adjusted for sex and age, was employed to assess the association between these genetic variants and severe clinical outcomes. <b>Results:</b> The results indicated that the <i>IL1B</i> rs16944-AG (OR: 1.98 [95% CI: 1.22–3.23], <i>p</i> = 0.006) and <i>TNF</i> rs1799964-CT (OR: 1.97 [95% CI: 1.22–3.22], <i>p</i> = 0.006) genotypes were associated with the need for hospitalization, while TNF rs1800630-AA (OR: 2.37 [95% CI: 1.08–5.33], <i>p</i> = 0.034) was associated with ICU admission. Additionally, the CC genotype of <i>TNF</i> rs1799964 was associated with a higher risk of mortality (OR: 3.73 [95% CI: 1.21–14.37], <i>p</i> = 0.034). <b>Conclusions:</b> Genetic variants—specifically <i>IL1B</i> rs16944 and rs1143627, and <i>TNF</i> rs1799964 and rs1800630—were associated with COVID-19 severity and should be further investigated in larger studies to evaluate their potential as predictive markers of severe outcomes in COVID-19.https://www.mdpi.com/2075-4418/15/11/1403SARS-CoV-2inflammatory responsegenetic polymorphismsdisease severityBrazilian population
spellingShingle Mariléa Furtado Feira
Renan Cesar Sbruzzi
Miriãn Ferrão Maciel-Fiuza
Vitória Carolina Griebeler
Tatiana Schaffer Gregianini
Letícia Garay Martins
Nathan Araujo Cadore
Jose Artur Bogo Chies
Thayne Woycinck Kowalski
Fernanda Sales Luiz Vianna
Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil
Diagnostics
SARS-CoV-2
inflammatory response
genetic polymorphisms
disease severity
Brazilian population
title Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil
title_full Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil
title_fullStr Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil
title_full_unstemmed Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil
title_short Association Between Genetic Variants in <i>TNF</i>, <i>IL6</i>, and <i>IL1B</i> Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil
title_sort association between genetic variants in i tnf i i il6 i and i il1b i genes and severity of covid 19 a cross sectional study of patients from southern brazil
topic SARS-CoV-2
inflammatory response
genetic polymorphisms
disease severity
Brazilian population
url https://www.mdpi.com/2075-4418/15/11/1403
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