ACE2 polymorphisms as potential players in COVID-19 outcome

Abstract

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.

Fig 1. MAF of the main polymorphisms in exons present in the most common isoforms (v1 and v2) of the ACE2 gene.

RS: Reference SNP; Ref: reference allele; Alt: alternative allele; EUR: European; EAS: East Asian; SAS: South Asia; AMR: Ad Mixed American; AFR: African; NAM: Native American; BAP: Brazilian Admixed Population; ABM: Online Archive of Brazilian Mutations.

Fig 2. MAF of polymorphisms of the 10k 5´ upstream region of ACE 2, with MAF differences greater than 1%.

Coordinate represents the frequency of the allele (MAF).

Fig 3. Minor allele frequency of the SNP intronic rs2285666 and rs4646140.