Analysis of ACE2 Genetic Variability Among Populations Highlights A Possible Link With COVID19-Related Neurological Complications

Abstract The Angiotensin-converting enzyme 2 (ACE2) has been recently recognized as the entry receptor of the novel pathogenic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2). The presence of structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and COVID19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of Single Nucleotide Variants (SNVs), Copy Number Variations (CNVs) and expression Quantitative Loci (eQTLs) in a cohort of 268 individuals representative of the Italian general population. The analysis identified 5 SNVs (rs35803318, rs41303171, rs774469453, rs773676270, rs2285666) which displayed a significantly different frequency distribution in the Italian cohort compared to the worldwide populations. The analysis of eQTLs located in and targeting ACE2, revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between the genetic variability of ACE2 and the neurological complications in patients with COVID19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.