AUTHOR=Tonon Federica , Tornese Gianluca , Giudici Fabiola , Nicolardi Francesca , Toffoli Barbara , Barbi Egidio , Fabris Bruno , Bernardi Stella 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.912064

DOI=10.3389/fendo.2022.912064

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>The cause of short stature remains often unknown. The renin-angiotensin system contributes to growth regulation. Several groups reported that angiotensin-converting enzyme 2 (<italic>ACE2</italic>)-knockout mice weighed less than controls. Our case-control study aimed to investigate if children with short stature had reduced <italic>ACE2</italic> expression as compared to controls, and its significance.</p></sec><sec><title>Materials and Methods</title><p>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. <italic>ACE</italic> and <italic>ACE2</italic> expression were measured in peripheral blood mononuclear cells, angiotensins were measured by ELISA.</p></sec><sec><title>Results</title><p>Children with short stature displayed significantly lower <italic>ACE2</italic> expression, being 0.40 fold induction (0.01-2.27) as compared to controls, and higher <italic>ACE/ACE2</italic>, with no differences between GHD and ISS. <italic>ACE2</italic> 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 <italic>ACE2</italic> expression was the value best predicting short stature, identifying correctly 70% of the children.</p></sec><sec><title>Conclusions</title><p>Our study confirms the association between the reduction of <italic>ACE2</italic> expression and growth retardation. Further studies are needed to determine its diagnostic implications.</p></sec>