New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis
New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis
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DOI：
10.1186/s12916-020-01673-z
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发表时间：
2020-07-15
期刊：
影响因子：
9.3
通讯作者：
Cheng, Feixiong
中科院分区：
文献类型：
--
作者：
Hou, Yuan;Zhao, Junfei;Cheng, Feixiong
背景资料：由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）现已在全球范围内得到确认。然而，COVID-19具有奇怪而可悲的选择性。COVID 19导致的发病率和死亡率随着年龄和共存的健康状况（包括癌症和心血管疾病）而急剧上升。人类遗传因素可能导致SARS-CoV-2的极高传播性，以及在一小部分但很大比例的感染个体中观察到的无情的疾病进展，但这些因素在很大程度上是未知的。在这项研究中，我们通过检测ACE 2和TMPRSS 2的DNA多态性来研究COVID-19的遗传易感性。（SARS-CoV-2的两个关键宿主因子）。我们在ACE 2和TMPRSS 2中发现了不同人群的独特遗传易感性。特别是，ACE 2多态性被发现与心血管和肺部疾病通过改变血管紧张素原-ACE 2相互作用，如p.Arg514Gly在非洲/非洲裔美国人的人口。TMPRSS 2中独特但普遍的多态性（包括p.Val160Met（rs 12329760），一种表达数量性状位点（eQTL）），为COVID-19的不同遗传易感性以及风险因素（包括癌症患者和男性患者的高危人群）提供了潜在的解释。我们进一步讨论了ACE 2或TMPRSS 2的多态性可以指导有效的治疗（即，结论：ACE 2或TMPRSS 2基因多态性可能与COVID-19的遗传易感性相关，因此需要开展人类遗传学研究以对抗COVID-19大流行。
Background: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown.Main body: In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from 81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19.Conclusion: This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.