Retinal changes as evidenced by fundoscopy and their frequencies in patients with COVID-19 with different variants of the angiotensin-converting enzyme gene

Authors

  • K. M. Hutsaliuk Volyn Regional Clinical Hospital
  • Z. I. Rossokha SI “Reference-centre for molecular diagnostic of Public Health Ministry of Ukraine”
  • N. Iu. Skalska Volyn Regional Clinical Hospital
  • N. A. Ulianova SI "The Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine" https://orcid.org/0000-0003-0802-240X

DOI:

https://doi.org/10.31288/oftalmolzh202415460

Keywords:

retina, fundoscopy, retinal changes, COVID-19, angiotensin converting enzyme (ACE) gene variants

Abstract

Purpose: To evaluate the relationship between angiotensin-converting enzyme (ACE; rs4340) gene variants and the retinal changes as evidenced by fundoscopy in patients with various clinical courses of COVID-19.
Material and Methods: Ninety-four COVID-19-positive patients (188 eyes) were included in the study. They had an extremely severe course, severe course, or moderately severe course of the disease with decompensated or compensated comorbidity. We evaluated the distribution of ACE ACE genotypes among patients and determined the retinal changes in COVID-19 patients with different ACE genotypes. Fundus images were obtained with a handheld fundus camera to identify clinically significant and insignificant retinal changes. A molecular and genetic study of ACE gene (rs4340) variants was carried out using allele-specific polymerase chain reaction (PCR). Statistical analysis of correlations between the course of COVID-19 and the presence of retinal changes as well as between the ACE gene variant and the presence of retinal changes was conducted.
Results: Among the analyzed individuals, 28 (29.6%), 47 (50.5%) and 19 (19.9%) were found to have the II genotype, ID genotype, and DD genotype, respectively. We found no significant correlation between metabolic status, severity of COVID-19 course and the ACE gene variant. No significant difference was found among groups of COVID-19 patients of different ACE genotypes with respect to the distribution of particular retinal changes. There was an increase (p < 0.001) in the risk of clinically significant retinal changes in patients with the DD genotype compared to patients with the II genotype and those with the ID genotype (p < 0.05).
Conclusion: The risk of clinically significant retinal changes is higher in COVID-19 patients with ACE genotype DD than in those with genotype II or ID (p < 0.001).

References

Kim Y-C, Jeong B-H. Strong correlation between the case fatality rate of COVID-19 and the rs6598045 single nucleotide polymorphism (SNP) of the interferon-induced transmembrane protein 3 (IFITM3) gene at the population-level. Genes (Basel) [Internet]. 2020;12(1):42. https://doi.org/10.3390/genes12010042

Aladawy SA, Adel LA, Abdel Salam SA, Raafat RH, Khattab MA. Polymorphism in promotor region of IL6 gene as a predictor for severity in COVID -19 patients. Egypt J Immunol [Internet]. 2022;29(2):1-9. https://doi.org/10.55133/eji.290201

Ponti G, Pastorino L, Manfredini M, Ozben T, Oliva G, Kaleci S, et al. COVID‐19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence. J Clin Lab Anal [Internet]. 2021;35(7). https://doi.org/10.1002/jcla.23798

Magusali N, Graham AC, Piers TM, Panichnantakul P, Yaman U, Shoai M, et al. A genetic link between risk for Alzheimer's disease and severe COVID-19 outcomes via the OAS1 gene. Brain [Internet]. 2021;144(12):3727-41. https://doi.org/10.1093/brain/awab337

Deb P, Zannat K-E-, Talukder S, Bhuiyan AH, Jilani MSA, Saif-Ur-Rahman KM. Association of HLA gene polymorphism with susceptibility, severity, and mortality of COVID‐19: A systematic review. HLA [Internet]. 2022;99(4):281-312. https://doi.org/10.1111/tan.14560

Tomita Y, Ikeda T, Sato R, Sakagami T. Association between HLA gene polymorphisms and mortality of COVID‐19: An in silico analysis. Immun Inflamm Dis [Internet]. 2020;8(4):684-94. https://doi.org/10.1002/iid3.358

Amoroso A, Magistroni P, Vespasiano F, Bella A, Bellino S, Puoti F, et al. HLA and AB0 polymorphisms may influence SARS-CoV-2 infection and COVID-19 severity. Transplantation [Internet]. 2021;105(1):193-200. https://doi.org/10.1097/TP.0000000000003507

Janssen R, Walk J. Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity. Med Hypotheses [Internet]. 2020;144(110218):110218. https://doi.org/10.1016/j.mehy.2020.110218

Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature [Internet]. 2020;579(7798):270-3. https://doi.org/10.1038/s41586-020-2012-7

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet [Internet]. 2020;395(10229):1033-4. https://doi.org/10.1016/S0140-6736(20)30628-0

Kumar M, Al Khodor S. Pathophysiology and treatment strategies for COVID-19. J Transl Med [Internet]. 2020;18(1). https://doi.org/10.1186/s12967-020-02520-8

Invernizzi A, Torre A, Parrulli S, Zicarelli F, Schiuma M, Colombo V, et al. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study. EClinicalMedicine [Internet]. 2020;27(100550):100550. https://doi.org/10.1016/j.eclinm.2020.100550

Order of the Ministry of Health of Ukraine of March 28, 2020 No. 722, https://www.dec.gov.ua/mtd/koronavirusna-hvoroba-2019-covid-19/

Clinical management of patients with COVID-19 "live" clinical guideline from 2021, https://www.dec.gov.ua/mtd/koronavirusna-hvoroba-2019-covid-19/

Rossokha ZI, Fishchuk LYe, Pokhylko VI, Cherniavska YuI, Tsvirenko SM, Kovtun SI, et al. The deletion variant of the CCR5 gene (rs333) but not the ACE gene (rs4340) is associated with long-term respiratory support in patients with COVID-19 pneumonia. Ukrainian Medical Journal. 2020;6(140):1-5. https://doi.org/10.32471/umj.1680-3051.140.195935

Management of patients with chronic retinal diseases in the current conditions of the COVID-19 pandemic in the world and in Ukraine. J Ophthalmol (Ukraine) [Internet]. 2021;91(2):82-4. https://doi.org/10.31288/oftalmolzh202128284

Aghsaeifard Z, Alizadeh R. The role of angiotensin-converting enzyme in immunity: Shedding light on experimental findings. Endocr Metab Immune Disord Drug Targets [Internet]. 2022;22(1):6-14. https://doi.org/10.2174/1871530321666210212144511

Li Y-P, Ma Y, Wang N, Jin Z-B. Eyes on coronavirus. Stem Cell Res [Internet]. 2021;51(102200):102200. https://doi.org/10.1016/j.scr.2021.102200

Hill JM, Clement C, Arceneaux L, Lukiw WJ. Angiotensin converting enzyme 2 (ACE2) expression in the aged brain and visual system. J Aging Sci. 2021;9(Suppl 7). https://doi.org/10.21203/rs.3.rs-296818/v1

Woods DR, Humphries SE, Montgomery HE. The ACE I/D polymorphism and human physical performance. Trends Endocrinol Metab [Internet]. 2000;11(10):416-20. https://doi.org/10.1016/S1043-2760(00)00310-6

Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest [Internet]. 1990;86(4):1343-6. https://doi.org/10.1172/JCI114844

Mohammadi F, Shahabi P, Zabani S, AA Z. Insertion/Deletion Gene Polymorphism and Serum Level of Angiotensin Converting Enzyme. TANAFFOS (Respiration). 2008; 7(2):18-22.

Patel DD, Parchwani DN, Dikshit N, Parchwani T. Analysis of the pattern, alliance and risk of rs1799752 (ACE I/D polymorphism) with essential hypertension. Indian J Clin Biochem [Internet]. 2022;37(1):18-28. https://doi.org/10.1007/s12291-020-00927-0

Pinheiro DS, Santos RS, Jardim PCBV, Silva EG, Reis AAS, Pedrino GR, et al. The combination of ACE I/D and ACE2 G8790A polymorphisms revels susceptibility to hypertension: A genetic association study in Brazilian patients. PLoS One [Internet]. 2019;14(8):e0221248. https://doi.org/10.1371/journal.pone.0221248

Liu M, Yi J, Tang W. Association between angiotensin converting enzyme gene polymorphism and essential hypertension: A systematic review and meta-analysis. J Renin Angiotensin Aldosterone Syst [Internet]. 2021;22(1):147032032199507. https://doi.org/10.1177/1470320321995074

Goyal A, Saluja A, Saraswathy KN, Bansal P, Dhamija RK. Role of ACE polymorphism in acute ischemic stroke. Neurol India [Internet]. 2021;69(5):1217-21. https://doi.org/10.4103/0028-3886.319217

Yoon CW, Kim J, Suh YJ, Kim BC, Youn YC, Jeong JH, et al. Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds. Front Neurol [Internet]. 2023;14. https://doi.org/10.3389/fneur.2023.1230141

Peretiahina D, Shakun K, Ulianov V, Ulianova N. The role of retinal plasticity in the formation of irreversible retinal deformations in age-related macular degeneration. Curr Eye Res [Internet]. 2022;47(7):1043-9. https://doi.org/10.1080/02713683.2022.2059810

Ahmad Mulyadi Lai HI, Chou S-J, Chien Y, Tsai P-H, Chien C-S, Hsu C-C, et al. Expression of endogenous angiotensin-converting enzyme 2 in human induced pluripotent stem cell-derived retinal organoids. Int J Mol Sci [Internet]. 2021;22(3):1320. https://doi.org/10.3390/ijms22031320

Hu K, Patel J, Swiston C, Patel BC. Ophthalmic Manifestations of Coronavirus (COVID-19). 2022 May 24. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. PMID: 32310553.

Downloads

Published

2024-02-29

How to Cite

1.
Hutsaliuk KM, Rossokha ZI, Skalska NI, Ulianova NA. Retinal changes as evidenced by fundoscopy and their frequencies in patients with COVID-19 with different variants of the angiotensin-converting enzyme gene. J.ophthalmol. (Ukraine) [Internet]. 2024 Feb. 29 [cited 2024 Apr. 29];(1):54-60. Available from: https://ua.ozhurnal.com/index.php/files/article/view/120

Issue

No. 1 (2024): Journal of Ophthalmology (Ukraine)

Section

Clinical Ophthalmology

License

Copyright (c) 2024 Hutsaliuk K. M., Rossokha Z. I., Skalska N. Iu., Ulianova N. A.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) that allows users to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author as long as they cite the source.

COPYRIGHT NOTICE

Authors who publish in this journal agree to the following terms:

  1. Authors hold copyright immediately after publication of their works and retain publishing rights without any restrictions.
  2. The copyright commencement date complies the publication date of the issue, where the article is included in.

DEPOSIT POLICY

  1. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) during the editorial process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work with an acknowledgement of its initial publication in this journal.
  3. Post-print (post-refereeing manuscript version) and publisher's PDF-version self-archiving is allowed.
  4. Archiving the pre-print (pre-refereeing manuscript version) not allowed.