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Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations

View ORCID ProfileRoberta Russo, View ORCID ProfileImmacolata Andolfo, View ORCID ProfileVito Alessandro Lasorsa, View ORCID ProfileAchille Iolascon, View ORCID ProfileMario Capasso
doi: https://doi.org/10.1101/2020.04.23.057190
Roberta Russo
1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
2CEINGE Biotecnologie Avanzate, Napoli, Italy
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Immacolata Andolfo
1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
2CEINGE Biotecnologie Avanzate, Napoli, Italy
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Vito Alessandro Lasorsa
1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
2CEINGE Biotecnologie Avanzate, Napoli, Italy
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Achille Iolascon
1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
2CEINGE Biotecnologie Avanzate, Napoli, Italy
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Mario Capasso
1Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
2CEINGE Biotecnologie Avanzate, Napoli, Italy
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  • For correspondence: mario.capasso@unina.it
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Abstract

The infection coronavirus disease 2019 (COVID-19) is caused by a virus classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At cellular level, virus infection initiates with binding of viral particles to the host surface cellular receptor angiotensin converting enzyme 2 (ACE2). SARS-CoV-2 engages ACE2 as the entry receptor and employs the cellular serine protease 2 (TMPRSS2) for S protein priming. TMPRSS2 activity is essential for viral spread and pathogenesis in the infected host. Understanding how TMPRSS2 protein expression in the lung varies in the population could reveal important insights into differential susceptibility to influenza and coronavirus infections. Here, we systematically analyzed coding-region variants in TMPRSS2 and the eQTL variants, which may affect the gene expression, to compare the genomic characteristics of TMPRSS2 among different populations. Our findings suggest that the lung-specific eQTL variants may confer different susceptibility or response to SARS-CoV-2 infection from different populations under the similar conditions. In particular, we found that the eQTL variant rs35074065 is associated with high expression of TMPRSS2 but with a low expression of the interferon (IFN)-α/β-inducible gene, MX1, splicing isoform. Thus, these subjects could account for a more susceptibility either to viral infection or to a decrease in cellular antiviral response.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 24, 2020.
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Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations
Roberta Russo, Immacolata Andolfo, Vito Alessandro Lasorsa, Achille Iolascon, Mario Capasso
bioRxiv 2020.04.23.057190; doi: https://doi.org/10.1101/2020.04.23.057190
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Genetic analysis of the novel SARS-CoV-2 host receptor TMPRSS2 in different populations
Roberta Russo, Immacolata Andolfo, Vito Alessandro Lasorsa, Achille Iolascon, Mario Capasso
bioRxiv 2020.04.23.057190; doi: https://doi.org/10.1101/2020.04.23.057190

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