key: cord-0684183-cohnyjp2
authors: Sama, Iziah E; Voors, Adriaan A
title: Men more vulnerable to COVID-19: explained by ACE2 on the X chromosome?
date: 2020-06-24
journal: Eur Heart J
DOI: 10.1093/eurheartj/ehaa526
sha: 1413373c5d6bce1397c64548e3eca8f23f93a745
doc_id: 684183
cord_uid: cohnyjp2

nan

The apparent superiority of women over men in not succumbing to COVID-19 is not completely understood. Therefore, examination of the sex-distinguishing genetics of angiotensin-converting enzyme 2 (ACE2), the host receptor that binds SARS coronaviruses, might help explain this sex disparity.

The ACE2 gene is located on the X chromosome and is expressed in various tissues, including the heart, kidneys, and testes. 1 Endogenous soluble ACE2 (found in the circulation) is shed from the cell membrane-bound form and the enzyme responsible for this shedding is ADAM17, 2,3 which is also membrane anchored. We recently postulated that the co-expression of ACE2 and ADAM17 in the testes (Supplementary figures 5 and 6 in Sama et al. 4 ) might partially explain why plasma ACE2 concentrations are higher in men than in women. 4 We agree with the commentary by Culebras and Hernández 5 that the mere occurrence of ACE2 on the X chromosome could also be important in explaining why men would suffer more from ACE2related diseases than women. In general, based on gene dosage, men suffer more often from X-linked disease traits than do women. 6 Future studies relating ACE2 levels to its genomic context, copy number variations, X-inactivation, and various co-morbidities and other (epi)genetic factors are required to improve our understanding of the gender-based disparities in ACE2-related pathophysiology and its relationship to the COVID-19 pandemic.

This work was supported by a grant from the European Commission (FP7-242209-BIOSTAT-CHF).

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