Background: Coronaviruses (CoV) are a large family of viruses that are common in people and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East Respiratory Syndrome (MERS-CoV), the Severe acute respiratory syndrome coronavirus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Many studies suggested that genetic variants in ACE2 gene may influence the host susceptibility/resistance to SARS-CoV-2 virus according to the functional role of ACE2 in human pathophysiology. However, all these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 99 Italian unrelated individuals clinically diagnosed with coronavirus disease 19 (COVID-19) to experimental demonstrate allelic association with disease severity. Methods: By whole-exome sequencing we analysed 99 DNA samples of severely and extremely severely COVID-19 patients hospitalized at the University Hospital of Rome Tor Vergata and Bambino Gesù Hospital in Rome. Results: We identified three different germline variants, one intronic (c.439+4G>A) and two missense (c.2158A>G, p.Asn720Asp; c.1888G>C, p.Asp630His ), in 26 patients with a similar frequency between male and female and a not statistically different frequency, except for c.1888G>C, (p.Asp630His) with the ethnically matched populations (EUR). Conclusions: Our results suggest that there is not any ACE2 exonic allelic association with disease severity. It is possible that rare susceptibility alleles are located in the non-coding region of the gene able to control ACE2 gene activity. It is therefore of interest, to explore the existence of ACE2 susceptibility alleles to SARS-Co-V2 in these regulatory regions. In addition, we found no significant evidence that ACE2 alleles is associated with disease severity/sex bias in the Italian population.

中文翻译：

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通过直接外显子组测序对99名SARS-CoV-2阳性患者中Covid-19和ACE2基因变异之间的等位基因关联没有证据

背景：冠状病毒（CoV）是人和许多动物物种中常见的一大类病毒。除了中东呼吸综合症（MERS-CoV），严重急性呼吸系统综合症冠状病毒（SARS-CoV）和现在的SARS-CoV-2外，动物冠状病毒很少感染人类，这是冠状病毒持续大流行的原因疾病2019（COVID-19）。许多研究表明，ACE2基因在人类病理生理中的功能作用可能会影响宿主对SARS-CoV-2病毒的易感性/耐药性。但是，所有这些研究都是基于流行病学和人口数据在计算机上进行的。因此，我们调查了在临床上被诊断出患有冠状病毒疾病19（COVID-19）的99名意大利无关个体的队列研究中ACE2变体的发生，以实验证明等位基因与疾病的严重程度相关。方法：通过全外显子组测序，我们分析了在罗马Tor Vergata大学医院和罗马BambinoGesù医院住院的重度和极重度COVID-19患者的99个DNA样本。结果：我们在26例患有ax病的男女之间的频率相似，但没有统计学差异，但c.1888G> C（p.Asp630His）和种族匹配的人口（EUR）除外。结论：我们的结果表明，没有ACE2外显子等位基因与疾病严重程度相关。罕见的易感性等位基因可能位于能够控制ACE2基因活性的基因的非编码区域。因此，有兴趣探索在这些调控区域中对SARS-Co-V2的ACE2易感性等位基因的存在。此外，我们没有发现重要的证据表明ACE2等位基因与意大利人群的疾病严重程度/性别偏见相关。