iScience (Apr 2021)

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

  • Immacolata Andolfo,
  • Roberta Russo,
  • Vito Alessandro Lasorsa,
  • Sueva Cantalupo,
  • Barbara Eleni Rosato,
  • Ferdinando Bonfiglio,
  • Giulia Frisso,
  • Pasquale Abete,
  • Gian Marco Cassese,
  • Giuseppe Servillo,
  • Gabriella Esposito,
  • Ivan Gentile,
  • Carmelo Piscopo,
  • Romolo Villani,
  • Giuseppe Fiorentino,
  • Pellegrino Cerino,
  • Carlo Buonerba,
  • Biancamaria Pierri,
  • Massimo Zollo,
  • Achille Iolascon,
  • Mario Capasso

Journal volume & issue
Vol. 24, no. 4
p. 102322

Abstract

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Summary: 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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