Genetic and epigenetic control of ACE2 expression and its possible role in COVID‐19

Lima, Rafael Silva; Rocha, Luiz Paulo Carvalho; Moreira, Paula Rocha

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is a pandemic that is claiming hundreds of thousands of lives around the world. Angiotensin‐converting enzyme‐2 (ACE2) is a key player in COVID‐19 due to its pivotal role in the SARS‐CoV‐2 infection. This enzyme is expressed throughout the body and the studies conducted so far have shown that its expression varies according to several factors, including cell type, sex, age, disease states and probably SARS‐CoV‐2 infection. Single‐nucleotide polymorphisms (SNPs) and epigenetic mechanisms, including DNA methylation, histone post‐translational modifications and microRNAs, impact ACE2 expression and may explain structural variation. The understanding of how genetic variants and epigenetic markers act to control ACE2 expression in health and disease states may contribute to comprehend several aspects of COVID‐19 that are puzzling researchers and clinicians. This review collects and appraises the literature regarding some aspects in the ACE2 biology, the expression patterns of this molecule, SNPs of the ACE2 gene and epigenetic mechanisms that may impact ACE2 expression in the context of COVID‐19.