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Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation.
Aging Cell. 2020 Jul; 19(7)AC

Abstract

The COVID-19 coronavirus is now spreading worldwide. Its pathogen, SARS-CoV-2, has been shown to use angiotensin-converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age-dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. 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. A shockingly common enrichment of viral infection pathways was found among ACE2 anti-expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). Our findings revealed a negative correlation between ACE2 expression and COVID-19 fatality at both population and molecular levels. These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general.

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Authors+Show Affiliations

Chen J
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China.
Jiang Q
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Xia X
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Liu K
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China.
Yu Z
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China.
Tao W
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China.
Gong W
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Han JJ
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China. CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

MeSH

Angiotensin-Converting Enzyme 2BetacoronavirusCOVID-19Computational BiologyCoronavirus InfectionsFemaleGene Expression RegulationGenetic VariationHumansMalePandemicsPeptidyl-Dipeptidase APneumonia, ViralReceptors, VirusSARS-CoV-2Testis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32558150

Citation

Chen, Jiawei, et al. "Individual Variation of the SARS-CoV-2 Receptor ACE2 Gene Expression and Regulation." Aging Cell, vol. 19, no. 7, 2020.
Chen J, Jiang Q, Xia X, et al. Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. Aging Cell. 2020;19(7).
Chen, J., Jiang, Q., Xia, X., Liu, K., Yu, Z., Tao, W., Gong, W., & Han, J. J. (2020). Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. Aging Cell, 19(7). https://doi.org/10.1111/acel.13168
Chen J, et al. Individual Variation of the SARS-CoV-2 Receptor ACE2 Gene Expression and Regulation. Aging Cell. 2020;19(7) PubMed PMID: 32558150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. AU - Chen,Jiawei, AU - Jiang,Quanlong, AU - Xia,Xian, AU - Liu,Kangping, AU - Yu,Zhengqing, AU - Tao,Wanyu, AU - Gong,Wenxuan, AU - Han,Jing-Dong J, Y1 - 2020/06/19/ PY - 2020/3/26/received PY - 2020/4/28/revised PY - 2020/5/11/accepted PY - 2020/6/20/pubmed PY - 2020/7/28/medline PY - 2020/6/20/entrez KW - ACE2 KW - COVID-19 KW - SARS-CoV2 JF - Aging cell JO - Aging Cell VL - 19 IS - 7 N2 - The COVID-19 coronavirus is now spreading worldwide. Its pathogen, SARS-CoV-2, has been shown to use angiotensin-converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age-dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. 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. A shockingly common enrichment of viral infection pathways was found among ACE2 anti-expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). Our findings revealed a negative correlation between ACE2 expression and COVID-19 fatality at both population and molecular levels. These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general. SN - 1474-9726 UR - https://www.unboundmedicine.com/medline/citation/32558150/Individual_variation_of_the_SARS_CoV_2_receptor_ACE2_gene_expression_and_regulation_ DB - PRIME DP - Unbound Medicine ER -