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01-12-2020 | Coronavirus | Correspondence

New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis

Authors: Yuan Hou, Junfei Zhao, William Martin, Asha Kallianpur, Mina K. Chung, Lara Jehi, Nima Sharifi, Serpil Erzurum, Charis Eng, Feixiong Cheng

Published in: BMC Medicine | Issue 1/2020

Abstract

Background

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown.

Main body

In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19.

Conclusion

This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.

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Title: New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis
Authors: Yuan Hou
Junfei Zhao
William Martin
Asha Kallianpur
Mina K. Chung
Lara Jehi
Nima Sharifi
Serpil Erzurum
Charis Eng
Feixiong Cheng
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Coronavirus
Chloroquin
Chloroquin
SARS-CoV-2
COVID-19
Hydroxychloroquine
Published in: BMC Medicine / Issue 1/2020
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-020-01673-z

At a glance: The STEP trials

Springer Medicine

New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis

Abstract

Background

Main body

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Main body

Conclusion

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