Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients: Human Genomics

A. Novelli, M. Biancolella, P. Borgiani, D. Cocciadiferro, V.L. Colona, M.R. D'Apice, P. Rogliani, S. Zaffina, F. Leonardis, A. Campana, M. Raponi, M. Andreoni, S. Grelli, G. Novelli

Research output: Contribution to journalArticlepeer-review


Background: 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. Methods: 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). Results: 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. Conclusions: 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. © 2020 The Author(s).
Original languageEnglish
JournalHum. Genomics
Issue number1
Publication statusPublished - 2020


  • ace2 protein
  • DNA
  • protein
  • unclassified drug
  • angiotensin converting enzyme 2
  • dipeptidyl carboxypeptidase
  • adolescent
  • adult
  • aged
  • allele
  • Article
  • carboxy terminal sequence
  • child
  • cohort analysis
  • controlled study
  • coronavirus disease 2019
  • DNA determination
  • female
  • gene frequency
  • genetic variability
  • human
  • Italy
  • major clinical study
  • male
  • pilot study
  • Severe acute respiratory syndrome coronavirus 2
  • whole exome sequencing
  • Betacoronavirus
  • computer simulation
  • Coronavirus infection
  • genetic predisposition
  • genetics
  • middle aged
  • pandemic
  • pathogenicity
  • very elderly
  • virology
  • virus pneumonia
  • young adult
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Computer Simulation
  • Coronavirus Infections
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Pandemics
  • Peptidyl-Dipeptidase A
  • Pneumonia, Viral
  • Whole Exome Sequencing
  • Young Adult


Dive into the research topics of 'Analysis of ACE2 genetic variants in 131 Italian SARS-CoV-2-positive patients: Human Genomics'. Together they form a unique fingerprint.

Cite this