1. Epistatic interaction of apolipoprotein E and lipolysis-stimulated lipoprotein receptor genetic variants is associated with Alzheimer's disease
- Author
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Samina Akbar, Ting Xie, Frances T. Yen, Christine Masson, Maria G. Stathopoulou, Thierry Oster, Sophie Visvikis-Siest, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), European Project, Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Service de Médecine Interne et Médecine Générale [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
- Subjects
Male ,0301 basic medicine ,Apolipoprotein E ,Aging ,Genotype ,Biology ,Polymorphism, Single Nucleotide ,Apolipoprotein E (APOE) ,03 medical and health sciences ,Apolipoproteins E ,0302 clinical medicine ,Gene Frequency ,Alzheimer Disease ,Genetic variation ,medicine ,Humans ,Allele ,Allele frequency ,Gene ,ComputingMilieux_MISCELLANEOUS ,Aged ,Receptors, Lipoprotein ,Genetics ,General Neuroscience ,Epistasis, Genetic ,Alzheimer's disease ,medicine.disease ,030104 developmental biology ,Epistasis ,Lipolysis stimulated lipoprotein receptor (LSR) ,Female ,lipids (amino acids, peptides, and proteins) ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Neurology (clinical) ,Geriatrics and Gerontology ,030217 neurology & neurosurgery ,Transcription Factors ,Developmental Biology ,Lipoprotein - Abstract
International audience; The ε4 allele of the apolipoprotein E (APOE) gene common polymorphism is the strongest genetic risk factor for Alzheimer's disease (AD). Human APOE gene is located on chromosome 19q13.1, a region linked to AD that also includes the LSR gene, which encodes the lipolysis-stimulated lipoprotein receptor (LSR). As an APOE receptor, LSR is involved in the regulation of lipid homeostasis in both periphery and brain. This study aimed to determine the potential interactions between 2 LSR genetic variants, rs34259399 and rs916147, and the APOE common polymorphism in 142 AD subjects (mean age: 73.16 ± 8.50 years) and 63 controls (mean age: 70.41 ± 8.49 years). A significant epistatic interaction was observed between APOE and both LSR variants, rs34259399 (beta = -0.95; p = 2 × 10-5) and rs916147 (beta = -0.83; p = 6.8 × 10-3). Interestingly, the interaction of LSR polymorphisms with APOE non-ε4 alleles increased AD risk. This indicates the existence of complex molecular interactions between these 2 neighboring genes involved in the pathogenesis of AD, which merits further investigation.Copyright © 2018 Elsevier Inc. All rights reserved.
- Published
- 2018