التفاصيل البيبلوغرافية
| العنوان: |
Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19. |
| المؤلفون: |
Muñiz-Banciella, María G.1 (AUTHOR), Albaiceta, Guillermo M.2,3,4,5,6 (AUTHOR), Amado-Rodríguez, Laura2,3,4,5,6 (AUTHOR), del Riego, Estefanía Salgado2 (AUTHOR), Alonso, Inés López3,5,6 (AUTHOR), López-Martínez, Cecilia3,5,6 (AUTHOR), Martín-Vicente, Paula3,5,6 (AUTHOR), García-Clemente, Marta3,4,7 (AUTHOR), Hermida-Valverde, Tamara7 (AUTHOR), Enríquez-Rodriguez, Ana I.7 (AUTHOR), Hernández-González, Cristina7 (AUTHOR), Cuesta-Llavona, Elías1,3 (AUTHOR), Alvarez, Victoria1,3 (AUTHOR), Gómez, Juan1,3 (AUTHOR), Coto, Eliecer1,3,4 (AUTHOR) eliecer.coto@sespa.es |
| المصدر: |
Immunogenetics. Apr2023, Vol. 75 Issue 2, p91-98. 8p. |
| مصطلحات موضوعية: |
*GENETIC variation, *COVID-19, *VIRUS diseases, *TYPE 1 diabetes, *RNA splicing, *INTERFERON receptors, *GENE expression |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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