Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis

Shitao Rao; Alexandria Lau; Hon-Cheong So

As discussed above, increased expression of ACE2 appears to be correlated with susceptibility to SARS-Cov and 201-nCoV infection. Nevertheless, the consequences of altered ACE2 expression may be rather complex. Kuba et al. reported that the Spike protein of the SARS-CoV down-modulated ACE2 expression 10 , which may lead to heightened risks of acute lung injury. Another study 41 suggested ACE2 may protect against acute pulmonary failure by blocking the renin-angiotensin signaling pathway. However, whether the same may apply to 2019-nCov is still unknown. If this is the case, then one may hypothesize that for unaffected individuals or those without (or with minimal) lung involvement yet (as could be the case for some subjects at the early stage of disease), a lower level of ACE2 expression on lung cells may be beneficial in reducing susceptibility to more sustained infection by reducing viral entry. However, for patients with severe lung involvement or at risk of acute lung injury, higher level of ACE2 expression may prevent risk of acute lung failure. Therefore, it may be clinically relevant to identify both types of drugs, i.e. those leading to elevated ACE2 expression as well as those leading to reduced expression. Further studies are warranted to clarify the role of ACE2 and whether drugs targeting ACE2 may be therapeutically useful.