Apolipoprotein E (ApoE) ε4 Genotype (ApoE rs429358-ApoE rs7412 Polymorphisms) Is Not Associated with Long COVID Symptoms in Previously Hospitalized COVID-19 Survivors

César Fernández-de-Las-Peñas; Lars Arendt-Nielsen; Gema Díaz-Gil; Francisco Gómez-Esquer; Antonio Gil-Crujera; Stella M Gómez-Sánchez; Silvia Ambite-Quesada; María A Palomar-Gallego; Oscar J Pellicer-Valero; Rocco Giordano

doi:10.3390/genes14071420

Apolipoprotein E (ApoE) ε4 Genotype (ApoE rs429358-ApoE rs7412 Polymorphisms) Is Not Associated with Long COVID Symptoms in Previously Hospitalized COVID-19 Survivors

Genes (Basel). 2023 Jul 10;14(7):1420. doi: 10.3390/genes14071420.

Affiliations

¹ Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, 28922 Alcorcón, Spain.
² Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark.
³ Department of Medical Gastroenterology, Mech-Sense, Aalborg University Hospital, DK-9000 Aalborg, Denmark.
⁴ Research Group GAMDES, Department of Basic Health Sciences, Universidad Rey Juan Carlos (URJC), 28922 Madrid, Spain.
⁵ Image Processing Laboratory (IPL), Universitat de València, Parc Científic, Paterna, 46100 València, Spain.

Abstract

The role of genetics as a predisposing factor related to an increased risk of developing long COVID symptomatology is under debate. The aim of the current secondary analysis was to identify the association between the Apolipoprotein E (ApoE) gene, a gene affecting cholesterol metabolism and previously associated with a higher risk of SARS-CoV-2 infection and COVID-19 severity, and the development of long COVID in a cohort of individuals who had been hospitalized by SARS-CoV-2 infection. Unstimulated whole saliva samples were collected from 287 previously hospitalized COVID-19 survivors. Three genotypes of the ApoE gene (ApoE ε2, ε3, ε4) were obtained based on the combination of ApoE rs429358 and ApoE rs7412 polymorphisms. Participants were asked to self-report the presence of any post-COVID symptom in a face-to-face interview at 17.8 ± 5.2 months after hospital discharge and medical records were obtained. Each participant reported 3.0 (1.9) post-COVID symptoms. Overall, no significant differences in long COVID symptoms were observed depending on the ApoE genotype (ApoE ε2, ApoE ε3, ApoE ε4). The presence of the ApoE ε4 genotype, albeit associated with a higher risk of SARS-CoV-2 infection and COVID-19 severity, did not appear to predispose for the presence of long COVID in our cohort of previously hospitalized COVID-19 survivors.

Keywords: ApoE; genotype; long COVID; single nucleotide polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apolipoprotein E2 / genetics
Apolipoprotein E4 / genetics
Apolipoproteins E* / genetics
COVID-19* / genetics
Genotype
Humans
Post-Acute COVID-19 Syndrome* / genetics
SARS-CoV-2

Substances

Apolipoprotein E2
Apolipoprotein E4
Apolipoproteins E

Grants and funding

The project was supported by a grant from the Novo Nordisk Foundation NNF21OC0067235 (Denmark) and by a grant associated to the Fondo Europeo De Desarrollo Regional—Recursos REACT-UE del Programa Operativo de Madrid 2014–2020, en la línea de actuación de proyectos de I+D+i en materia de respuesta a COVID 19 (LONG-COVID-EXP-CM). Both sponsors had no role in the design, collection, management, analyses, or interpretation of the data, draft, review, or approval of the manuscript or its content. The authors were responsible for the decision to submit the manuscript for publication, and the sponsor did not participate in this decision.