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Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19
MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associa...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9702716/ https://www.ncbi.nlm.nih.gov/pubmed/36434151 http://dx.doi.org/10.1007/s00251-022-01281-6 |
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author | Muñiz-Banciella, María G. Albaiceta, Guillermo M. Amado-Rodríguez, Laura del Riego, Estefanía Salgado Alonso, Inés López López-Martínez, Cecilia Martín-Vicente, Paula García-Clemente, Marta Hermida-Valverde, Tamara Enríquez-Rodriguez, Ana I. Hernández-González, Cristina Cuesta-Llavona, Elías Alvarez, Victoria Gómez, Juan Coto, Eliecer |
author_facet | Muñiz-Banciella, María G. Albaiceta, Guillermo M. Amado-Rodríguez, Laura del Riego, Estefanía Salgado Alonso, Inés López López-Martínez, Cecilia Martín-Vicente, Paula García-Clemente, Marta Hermida-Valverde, Tamara Enríquez-Rodriguez, Ana I. Hernández-González, Cristina Cuesta-Llavona, Elías Alvarez, Victoria Gómez, Juan Coto, Eliecer |
author_sort | Muñiz-Banciella, María G. |
collection | PubMed |
description | MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease. The MDA5/IFN pathway would play a critical role in the response to SARS-CoV-2 infection mediating the extent and severity of COVID-19. Here, we genotyped a cohort of 477 patients with critical ICU COVID-19 (109 death) for three IFIH1 functional variants: rs1990760 (p.Ala946Thr), rs35337543 (splicing variant, intron 8 + 1G > C), and rs35744605 (p.Glu627Stop). The main finding of our study was a significant increased frequency of rs1990760 C-carriers in early-onset patients (< 65 years) (p = 0.01; OR = 1.64, 95%CI = 1.18–2.43). This variant was also increased in critical vs. no-ICU patients and in critical vs. asymptomatic controls. The rs35744605 C variant was associated with increased blood IL6 levels at ICU admission. The rare rs35337543 splicing variant showed a trend toward protection from early-onset critical COVID-19. In conclusion, IFIH1 variants associated with reduced gene expression and lower IFN response might contribute to develop critical COVID-19 with an age-dependent effect. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00251-022-01281-6. |
format | Online Article Text |
id | pubmed-9702716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-97027162022-11-28 Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 Muñiz-Banciella, María G. Albaiceta, Guillermo M. Amado-Rodríguez, Laura del Riego, Estefanía Salgado Alonso, Inés López López-Martínez, Cecilia Martín-Vicente, Paula García-Clemente, Marta Hermida-Valverde, Tamara Enríquez-Rodriguez, Ana I. Hernández-González, Cristina Cuesta-Llavona, Elías Alvarez, Victoria Gómez, Juan Coto, Eliecer Immunogenetics Original Article MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease. The MDA5/IFN pathway would play a critical role in the response to SARS-CoV-2 infection mediating the extent and severity of COVID-19. Here, we genotyped a cohort of 477 patients with critical ICU COVID-19 (109 death) for three IFIH1 functional variants: rs1990760 (p.Ala946Thr), rs35337543 (splicing variant, intron 8 + 1G > C), and rs35744605 (p.Glu627Stop). The main finding of our study was a significant increased frequency of rs1990760 C-carriers in early-onset patients (< 65 years) (p = 0.01; OR = 1.64, 95%CI = 1.18–2.43). This variant was also increased in critical vs. no-ICU patients and in critical vs. asymptomatic controls. The rs35744605 C variant was associated with increased blood IL6 levels at ICU admission. The rare rs35337543 splicing variant showed a trend toward protection from early-onset critical COVID-19. In conclusion, IFIH1 variants associated with reduced gene expression and lower IFN response might contribute to develop critical COVID-19 with an age-dependent effect. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00251-022-01281-6. Springer Berlin Heidelberg 2022-11-25 2023 /pmc/articles/PMC9702716/ /pubmed/36434151 http://dx.doi.org/10.1007/s00251-022-01281-6 Text en © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Original Article Muñiz-Banciella, María G. Albaiceta, Guillermo M. Amado-Rodríguez, Laura del Riego, Estefanía Salgado Alonso, Inés López López-Martínez, Cecilia Martín-Vicente, Paula García-Clemente, Marta Hermida-Valverde, Tamara Enríquez-Rodriguez, Ana I. Hernández-González, Cristina Cuesta-Llavona, Elías Alvarez, Victoria Gómez, Juan Coto, Eliecer Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 |
title | Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 |
title_full | Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 |
title_fullStr | Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 |
title_full_unstemmed | Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 |
title_short | Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19 |
title_sort | age-dependent effect of the ifih1/mda5 gene variants on the risk of critical covid-19 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9702716/ https://www.ncbi.nlm.nih.gov/pubmed/36434151 http://dx.doi.org/10.1007/s00251-022-01281-6 |
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