Analysis of ACE2 Genetic Variants by Direct Exome Sequencing in 99 SARS-CoV-2 Positive Patients
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 coronavirus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Many studies have suggested that genetic variants in the ACE2gene may influence the host susceptibility or
... susceptibility or resistance to SARS-CoV-2 virus 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 99 Italian unrelated individuals clinically diagnosed with coronavirus disease 19 (COVID-19) to demonstrate a possible allelic association with COVID-19 by direct DNA analysis in a cohort of positive patients.MethodsWe analyzed, by whole-exome sequencing, 99 DNA samples of severe and extremely severe COVID-19 patients hospitalized at the University Hospital of Rome "Tor Vergata" and Bambino Gesù Children's Hospital, Rome.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 26 patients with a similar frequency in male and female. Thus far, only c.1888G>C p.(Asp630His) shows a statistically different frequency compared to the ethnically matched populations, suggesting that further research is needed to establish whether this variant is of functional significance.ConclusionsOur results suggest that there is no evidence of consistent ACE2 variants associated to the COVID-19. We hypothesize 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.