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. 2022 Jul 15:13:912064.
doi: 10.3389/fendo.2022.912064. eCollection 2022.

Children With Short Stature Display Reduced ACE2 Expression in Peripheral Blood Mononuclear Cells

Federica Tonon  1 , Gianluca Tornese  2 , Fabiola Giudici  3 , Francesca Nicolardi  1 , Barbara Toffoli  1 , Egidio Barbi  1   2 , Bruno Fabris  1   4 , Stella Bernardi  1   4
Affiliations

Children With Short Stature Display Reduced ACE2 Expression in Peripheral Blood Mononuclear Cells

Federica Tonon et al. Front Endocrinol (Lausanne). .

Abstract

Background: The cause of short stature remains often unknown. The renin-angiotensin system contributes to growth regulation. Several groups reported that angiotensin-converting enzyme 2 (ACE2)-knockout mice weighed less than controls. Our case-control study aimed to investigate if children with short stature had reduced ACE2 expression as compared to controls, and its significance.

Materials and methods: children aged between 2 and 14 years were consecutively recruited in a University Hospital pediatric tertiary care center. Cases were children with short stature defined as height SD ≤ -2 diagnosed with growth hormone deficiency (GHD) or idiopathic short stature (ISS), before any treatment. Exclusion criteria were: acute diseases, kidney disease, endocrine or autoimmune disorders, precocious puberty, genetic syndromes, SGA history. ACE and ACE2 expression were measured in peripheral blood mononuclear cells, angiotensins were measured by ELISA.

Results: Children with short stature displayed significantly lower ACE2 expression, being 0.40 fold induction (0.01-2.27) as compared to controls, and higher ACE/ACE2, with no differences between GHD and ISS. ACE2 expression was significantly and inversely associated with the risk of short stature, OR 0.26 (0.07-0.82), and it had a moderate accuracy to predict it, with an AUC of 0.73 (0.61-0.84). The cutoff of 0.45 fold induction of ACE2 expression was the value best predicting short stature, identifying correctly 70% of the children.

Conclusions: Our study confirms the association between the reduction of ACE2 expression and growth retardation. Further studies are needed to determine its diagnostic implications.

Keywords: ACE2; ANP; Renin-Angiotensin System; angiotensin; growth hormone deficiency; growth retardation; short stature.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
ACE2 expression and ACE/ACE2 ratio in children with short stature (CASES) and controls (CNT). Gene expression was measured as mRNA fold induction as compared to controls (CNT). ACE is for angiotensin converting enzyme, ACE2 is for angiotensin converting enzyme 2, GHD is for growth hormone deficiency and ISS is for idiopathic short stature. (A–D) Mann-Whitney test, (E–H) Kruskall-Wallis test.
Figure 2
Figure 2
ROC curves of ACE2 expression in predicting short stature. Accuracy of ACE2 expression as predictor of short stature.
See this image and copyright information in PMC

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