Coronaviruses (CoV) are a large family of viruses that are common in humans 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 corona virus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. However, many of 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 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesù Children’s Hospital, Rome. We used a large control group consisting of 1000 individuals (500 males and 500 females). We identified three different germline variants: one intronic c.439+4G>A and two missense c.1888G>C p.(Asp630His) and c.2158A>G p.(Asn720Asp) in a total of 131 patients with a similar frequency in male and female. Thus far, only the c.1888G>C p.(Asp630His) variant shows a statistically different frequency compared to the ethnically matched populations. Therefore, further studies are needed in larger cohorts, since it was found only in one heterozygous COVID-19 patient. Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.

中文翻译：

---

131名意大利SARS-CoV-2阳性患者中ACE2遗传变异的分析。

冠状病毒（CoV）是人类和许多动物中常见的一大类病毒。除中东呼吸综合征（MERS-CoV），严重急性呼吸综合征冠状病毒（SARS-CoV）以及现在SARS-CoV-2以外，动物冠状病毒很少感染人类，这是持续流行的原因。冠状病毒疾病2019（COVID-19）。几项研究表明，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感染的敏感性或耐药性。但是，许多这些研究都是根据流行病学和人口数据在计算机上进行的。因此，我们调查了131位在临床上被诊断为COVID-19的意大利无关人群和意大利对照人群中ACE2变异的发生，以通过直接DNA分析来评估与COVID-19可能的等位基因关联。作为一项初步研究，我们通过全外显子组测序分析了在罗马的Tor Vergata大学医院和BambinoGesù儿童医院住院的131例COVID-19患者的DNA样本中ACE2基因的遗传变异。我们使用了一个大型对照组，其中包括1000个人（500名男性和500名女性）。我们鉴定了三种不同的种系变体：在总共131例频率相似的患者中，一个内含子c.439 + 4G> A和两个错义c.1888G> C p。（Asp630His）和c.2158A> G p。（Asn720Asp）在男性和女性。到目前为止，只有c.1888G> C p。（Asp630His）变体与种族匹配的人群相比，显示出统计学上不同的频率。因此，由于仅在一名杂合型COVID-19患者中发现，因此需要在更大的队列中进行进一步研究。我们的结果表明，在我们的队列中，没有强有力的证据表明ACE2变体与COVID-19严重程度的一致性。我们可能会推测，罕见的易感性/抗性等位基因可能位于ACE2基因的非编码区，已知在基因活性的调节中起作用。ACE2变体与COVID-19严重程度的一致性相关性。我们可能会推测，罕见的易感性/抗性等位基因可能位于ACE2基因的非编码区，已知在基因活性的调节中起着作用。ACE2变体与COVID-19严重程度的一致性相关性。我们可能会推测，罕见的易感性/抗性等位基因可能位于ACE2基因的非编码区，已知在基因活性的调节中起作用。