ApoE ε4 carrier genotypes are associated with a significantly increased risk of COVID-19 (OR 1.44) and disease progression (OR 1.85) compared to non-ε4 carrier genotypes.
Meta-Analysis (n=646,388)
Does ApoE gene polymorphism (ε4 carrier genotypes) increase the risk and progression of COVID-19 compared to non-ε4 carrier genotypes?
ApoE4 is associated with increased risk and severity of COVID-19, potentially by downregulating ACE2 protein expression and causing dysregulation of the renin-angiotensin system.
Odds Ratio: 1.44 (95% CI 1.18–1.76)
p-value: p=0.0003
BACKGROUND: Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes. METHODS: A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression. RESULTS: ApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18-1.76) and progression (P < 0.00001, OR = 1.85, 95% CI 1.50-2.28) of COVID-19. ApoE interacts with both ACE2 and the spike protein but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7. CONCLUSIONS: ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin-angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.
Chen et al. (Thu,) conducted a meta-analysis in COVID-19 (n=646,388). ApoE4 carrier genotype vs. Non-ApoE4 carrier genotype was evaluated on Risk of COVID-19 (OR 1.44, 95% CI 1.18-1.76, p=0.0003). ApoE ε4 carrier genotypes are associated with a significantly increased risk of COVID-19 (OR 1.44) and disease progression (OR 1.85) compared to non-ε4 carrier genotypes.