Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation
Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation
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SARS-CoV-2受体ACE2基因表达和调控的个体差异
DOI：
10.1111/acel.13168
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发表时间：
2020-06-19
期刊：
影响因子：
7.8
通讯作者：
Han, Jing-Dong J.
中科院分区：
文献类型：
--
作者：
Chen, Jiawei;Jiang, Quanlong;Han, Jing-Dong J.
新冠肺炎冠状病毒目前正在全球范围内传播。其病原体SARS-CoV-2与2003年的严重急性呼吸综合征冠状病毒(SARS-CoV)一样，以血管紧张素转换酶2(ACE2)为宿主细胞受体。流行病学研究发现，尽管男性感染的可能性仅略高于女性，但在重病和死亡人数中占大多数，这也倾向于60岁以上或患有新陈代谢和心血管疾病的人。在这里，通过分析GTEx和其他涉及数千人的30个组织的公开数据，我们发现亚洲女性的ACE2表达水平显著高于亚洲女性，所有种族的ACE2表达水平都随着年龄的增长而下降，II型糖尿病患者中ACE2的表达显著下降。一直以来，导致ACE2高表达的最显著表达数量位点(EQTL)在东亚人中接近100%，比其他种族高30%。在ACE2反义表达基因中发现了病毒感染途径的异常丰富，病毒感染相关转录因子和性激素受体的多个结合位点位于ACE2调节区。人类和小鼠的数据分析进一步显示，在T2D患者和炎性细胞因子治疗中，ACE2的表达减少，并被雌激素和雄激素上调(两者都随着年龄的增长而减少)。我们的研究结果显示，无论是在群体水平还是在分子水平上，血管紧张素转换酶2的表达与新冠肺炎的死亡率都呈负相关。这些结果将有助于设计ACE2结合冠状病毒的潜在预防和治疗策略。
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.