{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:53:04Z","timestamp":1790488384215,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91749205"],"award-info":[{"award-number":["91749205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The COVID\u201019 coronavirus is now spreading worldwide. Its pathogen, SARS\u2010CoV\u20102, has been shown to use angiotensin\u2010converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS\u2010CoV) 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\u00a0years 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\u2010dependent 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, &gt;30% higher than other ethnic groups. A shockingly common enrichment of viral infection pathways was found among ACE2 anti\u2010expressed 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\u201019 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.<\/jats:p>","DOI":"10.1111\/acel.13168","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T10:41:22Z","timestamp":1592563282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":332,"title":["Individual variation of the SARS\u2010CoV\u20102 receptor ACE2 gene expression and regulation"],"prefix":"10.1111","volume":"19","author":[{"given":"Jiawei","family":"Chen","sequence":"first","affiliation":[{"name":"Peking\u2010Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanlong","family":"Jiang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Computational Biology CAS\u2010MPG 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Xia","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Computational Biology CAS\u2010MPG 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangping","family":"Liu","sequence":"additional","affiliation":[{"name":"Peking\u2010Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Peking\u2010Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Tao","sequence":"additional","affiliation":[{"name":"Peking\u2010Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Gong","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Computational Biology CAS\u2010MPG Partner Institute for Computational Biology Shanghai Institute of 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