Relationship between Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of COVID-19: A Meta-Analysis

Abstract

Introduction. Research shows the correlation between angiotensin-converting enzyme (ACE) deletion and insertion (D/I) polymorphism and COVID-19 risk; yet, conclusive evidence is still lacking. Thus, a meta-analysis of relevant articles was performed to more accurately estimate the relationship of ACE I/D polymorphism with the risk of COVID-19. Material and Methods. Relevant literature from the PubMed database was systematically reviewed, and odds ratios (ORs) and associated 95% confidence intervals (CIs) were measured. Additionally, the metapackage from Stata version 15.0 was used for statistical analysis. Results. The meta-analysis eventually contained 8 studies, including 1362 COVID-19 cases and 4312 controls. Based on the data, the ACE I/D polymorphism did not show an association with COVID-19 risk (D vs. I: $\text{OR}=1.25$ , 95% $\text{CI}=0.96–1.64$ ; DD vs. II: $\text{OR}=1.89$ , 95% $\text{CI}=0.95–3.74$ ; DI vs. II: $\text{OR}=1.75$ , 95% $\text{CI}=0.92–3.31$ ; dominant model: $\text{OR}=1.88$ , 95% $\text{CI}=0.99–3.53$ ; and recessive model: $\text{OR}=1.24$ , 95% $\text{CI}=0.81–1.90$ ). Further, subgroup analyses stratified based on case proved that the ACE D allele demonstrated an association with increasing risk of COVID-19 severity (D vs. I: $\text{OR}=1.64$ , 95% $\text{CI}=1.01–2.66$ ; DD vs. II: $\text{OR}=4.62$ , 95% $\text{CI}=2.57–8.30$ ; DI vs. II: $\text{OR}=3.07$ , 95% $\text{CI}=1.75–5.38$ ; dominant model: $\text{OR}=3.74$ , 95% $\text{CI}=2.15–6.50$ ; and recessive model: $\text{OR}=1.28$ , 95% $\text{CI}=0.46–3.51$ ). Conclusions. The ACE D allele was clearly related to an enhanced risk of COVID-19 severity. Hence, it is imperative to take into account the influence of genetic factors during the development of future vaccines.