TY - JOUR
T1 - ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels
T2 - A Mendelian randomization study: ACE inhibition and ACE2 expression
AU - Gill, Dipender
AU - Arvanitis, Marios
AU - Carter, Paul
AU - Hernández Cordero, Ana I.
AU - Jo, Brian
AU - Karhunen, Ville
AU - Larsson, Susanna C.
AU - Li, Xuan
AU - Lockhart, Sam M.
AU - Mason, Amy
AU - Pashos, Evanthia
AU - Saha, Ashis
AU - Tan, Vanessa Y.
AU - Zuber, Verena
AU - Bossé, Yohan
AU - Fahle, Sarah
AU - Hao, Ke
AU - Jiang, Tao
AU - Joubert, Philippe
AU - Lunt, Alan C.
AU - Ouwehand, Willem Hendrik
AU - Roberts, David J.
AU - Timens, Wim
AU - Van Den Berge, Maarten
AU - Watkins, Nicholas A.
AU - Battle, Alexis
AU - Butterworth, Adam S.
AU - Danesh, John
AU - Di Angelantonio, Emanuele
AU - Engelhardt, Barbara E.
AU - Peters, James E.
AU - Sin, Don D.
AU - Burgess, Stephen
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10 -4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
AB - Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10 -4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
KW - COVID-19
KW - Mendelian randomization
KW - angiotensin-converting enzyme inhibitors
KW - genetic epidemiology
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U2 - 10.1098/rsos.200958
DO - 10.1098/rsos.200958
M3 - Article
C2 - 33391794
AN - SCOPUS:85091304539
SN - 2054-5703
VL - 7
JO - Royal Society Open Science
JF - Royal Society Open Science
IS - 11
M1 - 0958
ER -