Angiotensin-converting enzyme 2 G8790A polymorphisms are associated with COVID-19 severity

In order to prevent COVID-19 from progressing, angiotensin-converting enzyme 2 (ACE2) binds to SARS-CoV-2 and prevents the virus from entering target cells. Several studies have found a correlation between COVID-19 risk and the ACE2 G8790A polymorphism; nevertheless, it remains inconclusive. A meta-analysis with relevant articles was carried out to more accurately estimate the risk of COVID-19.

We conducted a systematic review using PubMed, Embase, Cochrane Library, Scopus, Science Direct and Web of Science databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A meta-package was adopted in STATA version 12.0.

It was concluded that the ACE2 G8790A polymorphism was not associated with COVID-19 based on the data collected. Moreover, subgroup analyses stratified based on race proved that the ACE2 G allele showed association with increasing risk of COVID-19 severity in Asians (G vs A: OR = 4.07, 95% CI = 3.19-5.19; GG vs AA: OR = 10.01, 95% CI = 5.39-18.56; GA vs AA: OR = 3.57, 95% CI = 1.84-6.93; dominant model: OR = 8.05, 95% CI = 4.36-14.88; recessive model: OR = 3.83, 95% CI = 2.89-5.08).

The findings indicated that the G allele of ACE2 G8790A was related to an enhanced risk of COVID-19 severity in Asians. One possible reason is that ACE2 G allele was associated with a COVID-19 cytokine storm. Furthermore, Asians have higher levels of ACE2 transcripts than Caucasians and Africans. Therefore, a genetic factor should be considered when developing vaccines in the future.