Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19
Autor: | Ivan Gentile, Roberta Russo, Romolo Villani, Pellegrino Cerino, Vito Alessandro Lasorsa, Ferdinando Bonfiglio, Gabriella Esposito, Barbara Eleni Rosato, Giuseppe Fiorentino, Carmelo Piscopo, Giulia Frisso, Massimo Zollo, Achille Iolascon, Pasquale Abete, Biancamaria Pierri, Immacolata Andolfo, Carlo Buonerba, Giuseppe Servillo, Sueva Cantalupo, Gian Marco Cassese, Mario Capasso |
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Přispěvatelé: | Andolfo, Immacolata, Russo, Roberta, Lasorsa, Vito Alessandro, Cantalupo, Sueva, Rosato, Barbara Eleni, Bonfiglio, Ferdinando, Frisso, Giulia, Abete, Pasquale, Cassese, Gian Marco, Servillo, Giuseppe, Esposito, Gabriella, Gentile, Ivan, Piscopo, Carmelo, Villani, Romolo, Fiorentino, Giuseppe, Cerino, Pellegrino, Buonerba, Carlo, Pierri, Biancamaria, Zollo, Massimo, Iolascon, Achille, Capasso, Mario |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Science Genomics Single-nucleotide polymorphism Locus (genetics) 02 engineering and technology Disease Biology Genetic analysis Article 03 medical and health sciences Genetics MX1 Allele Gene TMPRSS2 Multidisciplinary SARS-CoV-2 COVID-19 021001 nanoscience & nanotechnology SNP genotyping 030104 developmental biology 0210 nano-technology |
Zdroj: | iScience iScience, Vol 24, Iss 4, Pp 102322-(2021) |
ISSN: | 2589-0042 |
DOI: | 10.1016/j.isci.2021.102322 |
Popis: | The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five SNPs correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target. Graphical Abstract |
Databáze: | OpenAIRE |
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