Preprint Article Version 1 This version is not peer-reviewed

Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov

Version 1 : Received: 3 February 2020 / Approved: 5 February 2020 / Online: 5 February 2020 (02:56:53 CET)
Version 2 : Received: 12 February 2020 / Approved: 14 February 2020 / Online: 14 February 2020 (04:32:49 CET)

How to cite: Cai, G. Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov. Preprints 2020, 2020020051 (doi: 10.20944/preprints202002.0051.v1). Cai, G. Tobacco-Use Disparity in Gene Expression of ACE2, the Receptor of 2019-nCov. Preprints 2020, 2020020051 (doi: 10.20944/preprints202002.0051.v1).

Abstract

In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed four large-scale datasets of normal lung tissue to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression. No significant disparities in ACE2 gene expression were found between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in smoker samples compared to non-smoker samples. This indicates the smokers may be more susceptible to 2019-nCov and thus smoking history should be considered in identifying susceptible population and standardizing treatment regimen.

Subject Areas

Wuhan 2019-nCov; ACE2; expression; susceptibility; race; age; gender; smoking

Comments (7)

Comment 1
Received: 6 February 2020
Commenter: Leo Hopkins
The commenter has declared there is no conflict of interests.
Comment: Very good article. One question - The article stipulates "tobacco smoking" - Question, do we know yet what in tobacco smoking causes the significant increase of ACE2 receptor sites and how does this compare with vapeing ? - In other words, is it the nicotine itself which causes the problem or other chemicals found in tobacco smoke that are not present in vaping? Also, does this ACE2 expression significantly reduce over time once a person quite smoking?
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Response 1 to Comment 1
Received: 7 February 2020
Commenter: Guoshuai Cai
The commenter has declared there is no conflict of interests.
Comment: Excellent questions, Leo. We currently have no clue on the causality. We are looking at the ACE2 expression in populations with different smoking histories and will publish the results soon. -Guoshuai
Response 2 to Comment 1
Received: 8 February 2020
Commenter: SFN
The commenter has declared there is no conflict of interests.
Comment: I second Leo Hopkins in wondering what it is about tobacco smoke that would increase ACE2 receptor sites, especially in light of other studies that indicate that exposure to cigarette smoke/nicotine upregulates ACE1 and actually downregulates ACE2, which is potentially the reason that tobacco use is associated with elevated blood pressure.

And isn't it also the case that there are legitimate, well-established differences in ACE2 allele frequencies (and thus gene expression) between those of different ethnicities?

Both of these factors would appear to indicate the opposite of what was found in this review. I will be very interested to see the results of further research on this topic.
Response 3 to Comment 1
Received: 13 February 2020
The commenter has declared there is no conflict of interests.
Comment: According to this article, it would appear that Nicotine may be the key agent in upregulating ACE2 expression: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295500/

So e-cigarettes, patches etc may be just as problematic as smoking in this regard.

This upregulation also has implications regarding blood pressure control, incidentally.
Response 4 to Comment 1
Received: 14 February 2020
Commenter: Guoshuai Cai
The commenter has declared there is no conflict of interests.
Comment: We have done the analysis on former smokers and current smokers in published the result in v2. We found Smokers especially former smokers have upregulated ACE2 in lung. Asian and Caucasian current smokers may have different expression of ACE2, which may indicate an existence of gene-smoking interaction.
Comment 2
Received: 9 February 2020
The commenter has declared there is no conflict of interests.
Comment: Hello, is there any study or statistics about levels of ace2 after one quits smoking? Or do you have any idea how much time it would need to see these levels drop?
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Response 1 to Comment 2
Received: 14 February 2020
Commenter: Guoshuai Cai
The commenter has declared there is no conflict of interests.
Comment: There question is interesting and important but might be complicated with gene-smoking interactions. It is discussed in the v2 paper, "Bulk and Single-Cell Transcriptomics Identify Tobacco-Use Disparity in Lung Gene Expression of ACE2, the Receptor of 2019-nCov".
Comment 3
Received: 9 February 2020
Commenter: Baran Ozmen
The commenter has declared there is no conflict of interests.
Comment: Can you refine your data to only include Han Chinese in the comparison between ACE2 expression? All critically sick seems to be Han Chinese no matter the passport.
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Response 1 to Comment 3
Received: 13 February 2020
The commenter has declared there is no conflict of interests.
Comment: Is it possible to clarify the relevance if this in asthmatics? Some smokers start of as slightly asthmatic but continue doing so through their life regardless. Others, share overlap with asthma and COPD. Is it specifically tobacco / smokers expressing ACE2 that's appear to be more susceptible or those who express it with other comorbidities?

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