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

Jiawei Chen; Quanlong Jiang; Xian Xia; Kangping Liu; Zhengqing Yu; Wanyu Tao; Wenxuan Gong; Jing-Dong J. Han

Working Paper Article Version 1 This version is not peer-reviewed

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

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.

COVID19; ACE2; SARS-CoV2

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

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