Abstract
BackgroundCoronaviruses (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.MethodsAs 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).ResultsWe 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.ConclusionsOur 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.
Highlights
Since the end of last year, in December 2019, Chinese authorities have reported several cases of pneumonia in Wuhan City, Hubei Province of China [1]
Several studies inferred that genetic variants in angiotensinconverting enzyme 2 (ACE2) gene may influence the individual susceptibility or resistance to SARS-CoV-2 according to the functional role of ACE2 in human pathophysiology [12]
It is possible that the affinity of binding of SARS-CoV-2 to ACE2 could be modulated by genetic variants within the receptor-binding domain (RBD) and/or other ACE2 domains
Summary
Since the end of last year, in December 2019, Chinese authorities have reported several cases of pneumonia in Wuhan City, Hubei Province of China [1]. Several studies inferred that genetic variants in ACE2 gene may influence the individual susceptibility or resistance to SARS-CoV-2 according to the functional role of ACE2 in human pathophysiology [12]. 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 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. Many of these studies have been conducted in silico based on epidemiological and population data. We 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
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