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Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19.
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.
  • Andolfo I; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Russo R; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Lasorsa VA; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Cantalupo S; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Rosato BE; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Bonfiglio F; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Frisso G; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Abete P; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Cassese GM; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Servillo G; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Esposito G; Dipartimento di Ingegneria chimica, dei Materiali e della Produzione industriale, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Gentile I; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Piscopo C; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Villani R; COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, Napoli, Italy.
  • Fiorentino G; COVID Hospital, P.O.S. Anna e SS. Madonna della Neve di Boscotrecase, Ospedali Riuniti Area Vesuviana, Napoli, Italy.
  • Cerino P; Dipartimento di Neuroscienze e Scienze riproduttive ed odontostomatologiche, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Buonerba C; Department of Molecular Medicine and Medical Biotechnologies, University of Naples, Federico II, 80145 Naples, Italy.
  • Pierri B; CEINGE Biotecnologie Avanzate, Via Gaetano Salvatore, 486, 80145 Napoli, Italy.
  • Zollo M; Dipartimento di Medicina clinica e Chirurgia, Università degli Studi di Napoli Federico II, Napoli, Italy.
  • Iolascon A; Medical and Laboratory Genetics Unit, A.O.R.N. 'Antonio Cardarelli', Napoli, Italy.
  • Capasso M; Poison Centre, A.O.R.N. 'Antonio Cardarelli', Napoli, Italy.
iScience ; 24(4): 102322, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1144743
ABSTRACT
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 single nucleotide polymorphisms (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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102322

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102322