Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul 11;18(7):e0288338.
doi: 10.1371/journal.pone.0288338. eCollection 2023.

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension

Onur Elbasan  1 , Feyza Bayram  2 , Ceyda Dinçer Yazan  1 , Tuğçe Apaydın  1 , Saida Dashdamirova  1 , Hamza Polat  2 , Ebru Arslan  2 , İpek Yılmaz  2 , Nastaran Karimi  2 , Buket Ertürk Şengel  3 , Sultan Seval Yılmaz  4 , Ömer Faruk Çelik  4 , Pınar Ata  2 , Goncagül Haklar  4 , Hülya Gözü  1
Affiliations

Angiotensin-Converting Enzyme (ACE) level, but not ACE gene polymorphism, is associated with prognosis of COVID-19 infection: Implications for diabetes and hypertension

Onur Elbasan et al. PLoS One. .

Abstract

Background: The renin-angiotensin-aldosterone system was shown to be activated in severe COVID-19 infection. We aimed to investigate the relationship between angiotensin converting enzyme (ACE) levels, ACE gene polymorphism, type 2 diabetes (T2DM), and hypertension (HT) and the prognosis of COVID-19 infection.

Methods: This cross-sectional study analyzed the clinical features of adult patients with SARS-CoV-2 infection. ACE gene analysis and ACE level measurements were performed. The patients were grouped according to ACE gene polymorphism (DD, ID or II), disease severity (mild, moderate, or severe), and the use of dipeptidyl peptidase-4 enzyme inhibitor (DPP4i), ACE-inhibitor (ACEi) or angiotensin receptor blocker (ARB). Intensive care unit (ICU) admissions and mortality were also recorded.

Results: A total of 266 patients were enrolled. Gene analysis detected DD polymorphism in the ACE 1 gene in 32.7% (n = 87), ID in 51.5% (n = 137), and II in 15.8% (n = 42) of the patients. ACE gene polymorphisms were not associated with disease severity, ICU admission, or mortality. ACE levels were higher in patients who died (p = 0.004) or were admitted to the ICU (p<0.001) and in those with severe disease compared to cases with mild (p = 0.023) or moderate (p<0.001) disease. HT, T2DM, and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission. ACE levels were similar in patients with or without HT (p = 0.374) and with HT using or not using ACEi/ARB (p = 0.999). They were also similar in patients with and without T2DM (p = 0.062) and in those with and without DPP4i treatment (p = 0.427). ACE level was a weak predictor of mortality but an important predictor of ICU admission. It predicted ICU admission in total (cutoff value >37.092 ng/mL, AUC: 0.775, p<0.001).

Conclusion: Our findings suggest that higher ACE levels, but not ACE gene polymorphism, ACEi/ARB or DPP4i use, were associated with the prognosis of COVID-19 infection. The presence of HT and T2DM and ACEi/ARB or DPP4i use were not associated with mortality or ICU admission.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Prediction of Mortality.
CRP, C-reactive protein; NLR, neutrophil/lymphocyte ratio; LDH, lactate dehydrogenase; ACE, angiotensin converting enzyme.
Fig 2
Fig 2. Prediction of Intensive Care Unit Admision.
CRP, C-reactive protein; NLR, neutrophil/lymphocyte ratio; ACE, angiotensin converting enzyme; CVA, cerebrovascular accident; LDH, lactate dehydrogenase.
See this image and copyright information in PMC

References

    1. Gunal O, Sezer O, Ustun GU, Ozturk CE, Sen A, Yigit S, et al.. Angiotensin-converting enzyme-1 gene insertion/deletion polymorphism may be associated with COVID-19 clinical severity: a prospective cohort study. Ann Saudi Med. 2021. May-Jun;41(3):141–146. doi: 10.5144/0256-4947.2021.141 Epub 2021 Jun 1. ; PMCID: PMC8176375. - DOI - PMC - PubMed
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al.. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020. Apr 16;181(2):271–280.e8. doi: 10.1016/j.cell.2020.02.052 Epub 2020 Mar 5. ; PMCID: PMC7102627. - DOI - PMC - PubMed
    1. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004. Jun;203(2):631–7. doi: 10.1002/path.1570 ; PMCID: PMC7167720. - DOI - PMC - PubMed
    1. Aung AK, Aitken T, Teh BM, Yu C, Ofori-Asenso R, Chin KL, et al.. Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study. J Infect. 2020. Dec;81(6):961–965. doi: 10.1016/j.jinf.2020.11.012 Epub 2020 Nov 14. ; PMCID: PMC7666537.) - DOI - PMC - PubMed
    1. Zheng H, Cao JJ. Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019. Am J Pathol. 2020. Oct;190(10):2013–2017. doi: 10.1016/j.ajpath.2020.07.009 Epub 2020 Jul 29. ; PMCID: PMC7387924. - DOI - PMC - PubMed