The Role of ACE, ACE2, and AGTR2 Polymorphisms in COVID-19 Severity and the Presence of COVID-19-Related Retinopathy

Genes (Basel). 2022 Jun 21;13(7):1111. doi: 10.3390/genes13071111.


The proposed SARS-CoV-2-induced dysregulation of the renin-angiotensin-aldosterone (RAAS) system results in endothelial dysfunction and microvascular thrombosis. The retinal plexuses contain terminal vessels without anastomotic connections, making the retina especially susceptible to ischemia. This study aimed to determine the role of selected polymorphisms of genes in the RAAS pathway in COVID-19 severity and their association with the presence of COVID-19 retinopathy. 69 hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities and 96 healthy controls were enrolled in this prospective cross-sectional study. The retina was assessed with fundus photography using a Topcon DRI OCT Triton (Topcon Corp., Tokyo, Japan) in the COVID-19 unit. Genotyping of selected polymorphisms in the genes for ACE (rs4646994), ACE2 (rs2285666), and AGTR2 (rs1403543) was performed. The COVID-19 group was divided into mild (n = 12) and severe (n = 57), and then further divided according to the presence of COVID-19 retinopathy (Yes, n = 50; No, n = 19). The presence of the AGTR2 rs1403543-AA genotype was associated with a 3.8-fold increased risk of COVID-19 retinopathy (p = 0.05). The genotype frequencies of selected gene polymorphisms were not significantly associated with either the presence of COVID-19 or its severity. This is the first study demonstrating a borderline association of the AGTR2 rs1403543-AA genotype with COVID-19 retinopathy in males; hence, the AGTR2 rs 1403543 A allele might represent a genetic risk factor for COVID-19 retinopathy in males.

Keywords: COVID-19; angiotensin II receptor type 2; angiotensin-converting enzyme; angiotensin-converting enzyme 2; polymorphism; retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • COVID-19* / complications
  • COVID-19* / genetics
  • Cross-Sectional Studies
  • Humans
  • Male
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Polymorphism, Genetic
  • Prospective Studies
  • Receptor, Angiotensin, Type 2
  • Retinal Diseases* / genetics
  • SARS-CoV-2


  • AGTR2 protein, human
  • Receptor, Angiotensin, Type 2
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

This study was partly supported by a grant from the Slovenian research agency (P3-0333).