The impact of ACE2 genetic polymorphisms (rs2106809 and rs2074192) on gender susceptibility to COVID-19 infection and recovery: A systematic review

Background: Epidemiological studies revealed there is a difference in susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of differences in gender with age and males being more inflicted. There is a clear indication that deaths caused by coronavirus disease 2019 (COVID-19) in males appeared at a higher rate than females across 35 nations. The implication of associated disease-risk genes, involved in the susceptibility of COVID-19 such as the angiotensin-converting enzyme 2 (ACE2), has recently received considerable attention due to their role in severe injury of lung and mediated SARS-CoV-2 entry as a host receptor. Objectives: Herein, we aimed to systematically review how two main genetic polymorphisms of ACE2 (rs2106809 and rs2074192) can affect the gender susceptibility to SARS-CoV-2 infection. Methods: To conduct this systematic review, a literature search in PubMed, Google Scholar, ScienceDirect, and Nature was made for the period 2004 to 2020. We searched for the impact of ACE2 genetic polymorphisms (rs2106809 and rs2074192) on gender susceptibility. Results: We noticed that there was a differential genotype distribution between males and females in various global populations whereas mutant variants were common in males compared to wild-type variants among females, which may reflect differences in gender susceptibility to infection with SARS-CoV-2. Females are less susceptible to coronavirus as compare to males because of the expression of ACE2 receptor. It has a double role in favour of COVID-19 and against COVID-19. Conclusions: Male mortality is greater than female mortality, which might be attributed to the ACE2 deficiency in women. Epidemiological studies have shown that the differences in sex and age have different susceptibility to SARS-CoV-2 infection.