The APOE ε4 allele is associated with a reduction in FEV1/FVC in women: A cross-sectional analysis of the Long Life Family Study

Abstract

IntroductionMurine studies have shown that apolipoprotein E modulates pulmonary function during development, aging, and allergen-induced airway disease. It is not known whether the polymorphic human APOE gene influences pulmonary function.ObjectivesWe assessed whether an association exists between the polymorphic human APOE ε2, ε3, and ε4 alleles and pulmonary function among participants in the Long Life Family Study.MethodsData from 4,468 Caucasian subjects who had genotyping performed for the APOE ε2, ε3, and ε4 alleles were analyzed, with and without stratification by sex. Statistical models were fitted considering the effects of the ε2 allele, defined as ε2/2 or ε2/3 genotypes, and the ε4 allele, defined as ε3/4 or ε4/4 genotypes, which were compared to the ε3/3 genotype.ResultsThe mean FEV1/FVC ratio (the forced expiratory volume in one second divided by the forced vital capacity) was lower among women with the ε4 allele as compared to women with the ε3/3 genotype or the ε2 allele. Carriage of the APOE ε4 allele was associated with FEV1/FVC, which implied lower values. Further analysis showed that the association primarily reflected women without lung disease who were older than 70 years. The association was not mediated by lipid levels, smoking status, body mass index, or cardiovascular disease.ConclusionsThis study for the first time identifies that the APOE gene is associated with modified lung physiology in women. This suggests that a link may exist between the APOE ε4 allele, female sex, and a reduction in the FEV1/FVC ratio in older individuals.

Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK Biobank

“…Our observation of reduced odds of chronic liver disease and cirrhosis provides experimental support for the findings of a recent literature review suggesting the e4 allele has protective effects in the progression of liver cirrhosis [18]. Although spirometric measures of lung function provided limited support for the protective effect we observed between the e4e4 genotype and chronic airway obstruction (also known as chronic obstructive pulmonary disease, COPD), our findings add to previous observations of marginally increased lung function in e4 carriers [19], strengthening the suggestion of an underlying difference in lung physiology.…”

COVID-19 enters the expanding network of apolipoprotein E4-related pathologies

“…The major influence of APOE4 on lipid metabolism, however, does not exclude the possibility that other APOE4 functions in the lung impact the clinical outcome of SARS-CoV-2 infection. In this regard, the APOE ε4 allele has been associated with reduced lung respiratory capacity in the elderly irrespective of lipid levels [ 107 ], and apoe ablation in the mouse is associated with the development of severe pulmonary hypertension [ 108 ], which increases the risk of death in COVID-19 patients.…”

Residence, Clinical Features, and Genetic Risk Factors Associated with Symptoms of COVID-19 in a Cohort of Older People in Madrid

“…The role of APOE in viral infections seems to be due to its binding to heparan sulfate proteoglycans (HSPG), functioning either as a Trojan horse (HCV) or competing for the binding to the HSPG with the viral particles (HSV and HIV). APOE is expressed in lung cells modulating normal lung health and the pathogenesis of respiratory diseases, including asthma, acute lung injury, cancer, emphysema, pulmonary fibrosis, and pulmonary hypertension [ 31 , 32 ]. Interestingly, although the SARS-CoV-2 enters into the cell by the binding of the viral spike protein to the ACE2 cellular receptor, the initial attachment seems to be facilitated by the binding of this protein to the cell surface HSPGs [ 33 ].…”