COVID-19 enters the expanding network of apolipoprotein E4-related pathologies
Kalliopi Gkouskou,
Theodora Vasilogiannakopoulou,
Evangelos Andreakos,
Nikolaos Davanos,
Maria Gazouli,
Despina Sanoudou,
Aristides G. Eliopoulos
Affiliations
Kalliopi Gkouskou
Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Embiodiagnostics Biology Research Company, Heraklion, Crete, Greece; Corresponding author. Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, 11527, Greece.
Theodora Vasilogiannakopoulou
Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Evangelos Andreakos
Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Nikolaos Davanos
ANTISEL S.A., Athens, Greece
Maria Gazouli
Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Despina Sanoudou
Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Clinical Genomics and Pharmacogenomics Unit, 4th Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Greece; Center for New Biotechnologies and Precision Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Aristides G. Eliopoulos
Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Center for New Biotechnologies and Precision Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Corresponding author. Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, 11527, Greece.
COVID-19 incidence and case fatality rates (CFR) differ among ethnicities, stimulating efforts to pinpoint genetic factors that could explain these phenomena. In this regard, the multiallelic apolipoprotein E (APOE) gene has recently been interrogated in the UK biobank cohort, demonstrating associations of the APOE ε4/ε4 genotype with COVID-19 severity and mortality. The frequency of the ε4 allele and thus the distribution of APOE ε4/ε4 genotype may differ among populations. We have assessed APOE genotypes in 1638 Greek individuals, based on haplotypes derived from SNP rs7412 and rs429358 and found reduced frequency of ε4/ε4 compared to the British cohort. Herein we discuss this finding in relation to CFR and hypothesize on the potential mechanisms linking APOE ε4/ε4 to severe COVID-19. We postulate that the metabolic deregulation ensued by APOE4, manifested by elevated cholesterol and oxidized lipoprotein levels, may be central to heightened pneumocyte susceptibility to infection and to exaggerated lung inflammation associated with the ε4/ε4 genotype. We also discuss putative dietary and pharmacological approaches for the prevention and management of COVID-19 in APOE ε4/ε4 individuals.
