The APOE e4 allele is associated with a reduction in FEV 1 /FVC in women: A cross-sectional analysis of the long life family study

Alexander M. Kulminski, Amisha V. Barochia, Yury Loika, Nalini Raghavachari, Konstantin G. Arbeev, Mary K. Wojczynski, Bharat Thyagarajan, Badri N. Vardarajan, Kaare Christensen, Anatoliy I. Yashin, Stewart J. Levine

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Abstract

Introduction Murine 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. Objectives We 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. Methods Data 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. Results The mean FEV 1 /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 FEV 1 / 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. Conclusions This 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 FEV 1 /FVC ratio in older individuals.

Original languageEnglish (US)
Article numbere0206873
JournalPloS one
Volume13
Issue number11
DOIs
StatePublished - Nov 2018

Bibliographical note

Funding Information:
The Long Life Family Study is funded by U01AG023749, U01AG023744, U01AG049508 and U01AG023712 from the National Institute on Aging, NIH, USA. This work was supported by the National Institute on Aging (grant numbers U01 AG023712, P01 AG043352, R01 AG047310) and the Division of Intramural Research, NHLBI (1ZIAHL006053-08), NIH, USA. The funding source did not participate in the writing of the manuscript or the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Kaare Christensen, Anatoliy I. Yashin.

Publisher Copyright:
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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