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Review
. 2020 Oct;190(10):2013-2017.
doi: 10.1016/j.ajpath.2020.07.009. Epub 2020 Jul 29.

Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019

Haoyi Zheng  1 , J Jane Cao  2
Affiliations
Review

Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019

Haoyi Zheng et al. Am J Pathol. 2020 Oct.

Abstract

Coronavirus disease 2019 has markedly varied clinical presentations, with most patients being asymptomatic or having mild symptoms. However, severe acute respiratory disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is common and associated with mortality in patients who require hospitalization. The etiology of susceptibility to severe lung injury remains unclear. Angiotensin II, converted by angiotensin-converting enzyme (ACE) from angiotensin I and metabolized by ACE 2 (ACE2), plays a pivotal role in the pathogenesis of lung injury. ACE2 is identified as an essential receptor for SARS-CoV-2 to enter the cell. The binding of ACE2 and SARS-CoV-2 leads to the exhaustion and down-regulation of ACE2. The interaction and imbalance between ACE and ACE2 result in an unopposed angiotensin II. Considering that the ACE insertion (I)/deletion (D) gene polymorphism contributes to the ACE level variability in general population, in which mean ACE level in DD carriers is approximately twice that in II carriers, we propose a hypothesis of genetic predisposition to severe lung injury in patients with coronavirus disease 2019. It is plausible that the ACE inhibitors and ACE receptor blockers may have the potential to prevent and to treat the acute lung injury after SARS-CoV-2 infection, especially for those with the ACE genotype associated with high ACE level.

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Figures

Figure 1
Figure 1
Illustration of the impact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has on the main metabolic pathways driven by angiotensin-converting enzyme (ACE) and ACE2 in the renin-angiotensin system, proposed mechanisms of ACE DD genotype in the severe lung injury of coronavirus disease 2019, and the potential impact of ACE DD genotype in the high-risk population. The potential therapeutic targets for ACE inhibitors (ACEIs) and angiotensin (AT) 1 receptor blockers (ARBs) are also shown.
See this image and copyright information in PMC

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