Working Paper Article Version 1 This version is not peer-reviewed

Individual Variation of the SARS-CoV2 Receptor ACE2 Gene Expression and Regulation

Version 1 : Received: 11 March 2020 / Approved: 12 March 2020 / Online: 12 March 2020 (03:15:15 CET)

How to cite: Chen, J.; Jiang, Q.; Xia, X.; Liu, K.; Yu, Z.; Tao, W.; Gong, W.; Han, J.J. Individual Variation of the SARS-CoV2 Receptor ACE2 Gene Expression and Regulation. Preprints 2020, 2020030191 Chen, J.; Jiang, Q.; Xia, X.; Liu, K.; Yu, Z.; Tao, W.; Gong, W.; Han, J.J. Individual Variation of the SARS-CoV2 Receptor ACE2 Gene Expression and Regulation. Preprints 2020, 2020030191

Abstract

The COVID19 coronavirus SARS-CoV2 spreading in Wuhan and now worldwide has been shown to use angiotensin-converting enzyme 2 ACE2 as its host cell receptor, like the severe acute respiratory syndrome coronavirus (SARS-CoV). Epidemiology studies found different sex and age groups have different susceptibility to infection, and very skewed severity and mortality of the virus infection, with male, old age, and comorbidity being the most inflicted. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found significantly higher expression in Asian females compared to males and other ethnic groups, an age dependent ACE2 expression decrease and a highly significant decrease in type II diabetic patients. Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. Together with the shockingly common enrichment of viral infection pathways among ACE2 anti-expressed genes, binding of virus infection-related transcription factors at ACE2 regulatory regions, the repression of ACE2 expression by inflammatory cytokines and by type 2 diabetes, and the induction by estrogen and androgen (both decrease with age) established a negative correlation between ACE2 expression and CovID19 fatality at both population and molecular levels. Our results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general.

Keywords

COVID19; ACE2; SARS-CoV2

Subject

Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Comments (0)

Comment 1
Received: 19 March 2020
Commenter: Robert W Walters
The commenter has declared there is no conflict of interests.
Comment: I think the article is great. However, the supplemental download does not contain the supplemental tables.
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Comment 2
Received: 5 April 2020
Commenter: Jane Davies
The commenter has declared there is no conflict of interests.
Comment: Hi

Thank you for your article and it supports my reason for looking in to this too. I sent an article to Oxford who are conducting trials in UK as I found this report done 3 years ago and I came to a conclusion that there is a correlation with estrogen and also the thymus. Hope this is of help in this fight against COVID 19.



From: Jane Davies Sent: 30 March 2020 16:06
To: Ruth Davis Subject: Thymus and estrogen effects on COVID 19



Dear Ruth



Hopefully you are aware of this anyway - basic science but have found some interesting reports. The questions constantly being asked are why no children severely affected and why more men than women seem to succumb to this virus.



My first thought was,



Is the Thymus the main protector especially in children as it is at its largest before puberty. It has been found that other virus have entered the thymus. Does this adequately destroy the virus and what effect does the virus have on the Thymus? As the thymus shrinks over time then this could explain why the virus is more serious in older patients.



The other thoughts were the effect of estrogen on ACE2 and found a report that supports this. The report also suggests that HRT reduced older females risk to AF and it seemed that maybe this could be investigated further as the report is a few years old now.



Many thanks



kind regards



Jane Davies

https://www.endocrineweb.com/endocrinology/overview-thymus

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.0020062
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544171/
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0127515&type=printable
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