Men more vulnerable to COVID-19: explained by ACE2 on the X
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The apparent superiority of women over men in not succumbing to COVID-19 is not completely understood. Therefore, the 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. Endogenous soluble ACE2 (found in the circulation) is shed from the cell membrane-bound form and the enzyme responsible for this shedding is ADAM which is also membrane-anchored. Researchers recently postulated that the co-expression of ACE2 and ADAM17 in the testes might partially explain why plasma ACE2 concentrations are higher in men than in women. In general, based on gene dosage, men suffer more often from X-linked disease traits than do women.

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.

Source: https://academic.oup.com/eurheartj/article/41/32/3096/5861742
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