Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations

By Yanan Cao, Lin Li, Zhimin Feng, Shengqing Wan, Peide Huang, Xiaohui Sun, Fang Wen, Xuanlin Huang, G. Ning, Weiqing Wang. Cell Discovery, 2020

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Dear Editor, The ACE2 gene encodes the angiotensin-converting enzyme-2, which has been proved to be the receptor for both the SARS-coronavirus (SARS-CoV) and the human respiratory coronavirus NL63. Recent studies and analyses indicate that ACE2 could be the host receptor for the novel coronavirus 2019-nCoV/SARS-CoV-2. Previous studies demonstrated the positive correlation of ACE2 expression and the infection of SARS-CoV in vitro. A number of ACE2 variants could reduce the association between ACE2 and S-protein in SARS-CoV or NL63. Therefore, the expression level and expression pattern of human ACE2 in different tissues might be critical for the susceptibility, symptoms, and outcome of 2019-nCoV/SARS-CoV-2 infection. A recent single-cell RNA-sequencing (RNA-seq) analysis indicated that Asian males may have higher expression of ACE2. Currently, the clinical reports of 2019nCoV/SARS-CoV-2 infection from non-Asian populations for comparison are very limited. A study from Munich reported four German cases, all of which showed mild clinical symptoms without severe illness. However, the genetic basis of ACE2 expression and function in different populations is still largely unknown. Therefore, genetic analysis of expression quantitative trait loci (eQTLs) and potential functional coding variants in ACE2 among populations are required for further epidemiological investigations of 2019-nCoV/SARS-CoV-2 spreading in East Asian (EAS) and other populations. To systematically investigate the candidate functional coding variants in ACE2 and the allele frequency (AF) differences between populations, we analyzed all the 1700 variants (Supplementary Table S1) in ACE2 gene region from the ChinaMAP (China Metabolic Analytics Project, under reviewing) and 1KGP (1000 Genomes Project) databases. The AFs of 62 variants located in the coding regions of ACE2 in ChinaMAP, 1KGP, and other largescale genome databases were summarized (Supplementary Table S2). All of the 32 variants potentially affecting the amino acid sequence of ACE2 in databases were shown (Fig. 1a). Previous study showed that the residues near lysine 31, and tyrosine 41, 82–84, and 353–357 in human ACE2 were important for the binding of S-protein in coronavirus. The mutations in these residues were not found in different populations in our study. Only a singleton truncating variant of ACE2 (Gln300X) was identified in the ChinaMAP (Fig. 1a). These data suggested that there was a lack of natural resistant mutations for coronavirus S-protein binding in populations. The effects of low-frequency missense variants in populations for S-protein binding could be further investigated. The distributions of seven hotspot variants (Lys26Arg, Ile468Val, Ala627Val, Asn638Ser, Ser692Pro, Asn720Asp, and Leu731Ile/Leu731Phe) in different populations were shown (Fig. 1b). Six low-frequency loci (rs200180615, rs140473595, rs199951323, rs147311723, rs149039346, and rs73635825) were found to be specific in 1KGP database, the AFs of which were also low in the gnomAD and TopMed database. Only two of these six variants (rs200180615 and rs140473595) could be found in CHB (Han Chinese in Beijing) population with the AF < 0.01.

Subfields: Computational Theory and Mathematics, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/53eccda7977a31e3d0f565c884da036b1e85438e

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Citations in the corpus

Immunology of COVID-19: Current State of the Science (2020, positive): “identified variants that are potentially expression quantitative trait loci (eQTL) of ACE2 (i.e. they may potentially alter ACE2 gene expression) and analyzed their frequencies in different populations (Cao et al., 2020c) .”
Clinical and epidemiological characteristics of 1420 European patients with mild‐to‐moderate coronavirus disease 2019 (2020, background): “A recent comparison of the 15 expression quantitative trait loci (eQTLs) variants of the ACE2 gene suggested different ACE2 polymorphisms and expression levels between Asian and European populations [17].”
A Review of SARS-CoV-2 and the Ongoing Clinical Trials (2020, background): “The indistinguishable susceptibility between individuals can be another reason for the rapid spread of SARS-CoV-2 across continents and different human populations [38] .”
Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study (2020, background): “According to these studies, it is conceivable that the diversity of ACE2 expression pattern in Asian and European populations could be an important track that needs further investigation.”