Angiotensin-converting enzyme (ACE1, ACE2) gene variants are associated with COVID19 severity depending on the hypertension status
Abstract
Background
The Angiotensin system is implicated in the pathogenesis of COVID19. First, ACE2 is the cellular receptor for SARS-COv-2, and expression of theACE2gene could regulate the individual’s susceptibility to infection. In addition, the balance between ACE1 and ACE activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID19. FunctionalACE1/ACE2gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID19.
Methods
We studied 204 COVID19 patients (137 non-severe and 67severe-ICU cases) and 536 age-matched controls. TheACE1insertion/deletion andACE2rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients.
Results
Severe COVID19 was associated with hypertension male gender (p<0.001), hypertension (p=0.006), hypercholesterolaemia (p=0.046), and the ACE1-DD genotype (p=0.049). In the multiple logistic regression hypertension (p=0.02, OR=2.26, 95%CI=1.12-4.63) and male gender (p=0.002; OR=3.15, 95%CI=1.56-6.66) remained as independent significant predictors of severity. TheACE2polymorphism was not associated with the disease outcome. TheACE2sequencing showed no coding sequence variants that could explain an increased risk of developing COVID19.
Conclusions
Adverse outcome of COVID19 was associated with male gender, hypertension, hypercholesterolemia and theACE1genotype. TheACE1-I/D was a significant risk factor for severe COVID19, but the effect was dependent on the hypertensive status.
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