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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.

International audience; Telomere length has been subject of studies for many decades, aiming to elucidate its role in physiological processes, in process of aging and in diverse pathologies. Yet today, there is still no "big title" discovery that would lead to a practical use of telomeres as a reliable biomarker or target for a new drug. However, therapies for chronic disease patients are being tested and companies are already offering commercial tests for telomere length measurement. The strong genetic heritability of telomeres is opening the place for pharmacogenomics researches that could promote the personalized treatment of diverse diseases. In this article, we present the recent knowledge of telomeres genetic determination obtained by genome-wide association studies (GWAS), important biomarkers related to telomere length and review the possibilities of telomere's practical implementation in the medical treatment of diverse diseases and as a potential biomarker in personalized medicine. Furthermore, we summarise commercial offers of telomere length measurements available and we discuss the actions that should be taken to make steps forward into final application of the accumulated knowledge into practical use.

International audience; Although recent studies have demonstrated a link between environmental contaminants exposure and obesity, the molecular mechanisms remain to be determined. Reduced expression of the hepatic lipolysis stimulated lipoprotein receptor (LSR), which is important for chylomicron clearance, is associated with increased body fat mass in mice. Since the polycylic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is associated with weight gain in mice, the objective of this study was to determine if B[a]P modified hepatic LSR and lipid status. In 11-wk old male C57BL/6RJ mice treated with B[a]P (0.5 mg/kg, i.p. every 48h, 15 days), the increased weight gain was associated with increased plasma triglycerides and cholesterol, and increased liver cholesterol content as compared to control mice. LDL-receptor protein was decreased, and the positive correlation between hepatic LSR and LDL-receptor protein in control animals was absent in the B[a]P-treated mice, pointing towards a dysregulation of hepatic lipid homeostasis in the mice exposed to this pollutant. Hepa1-6 cells treated with 0.001 mM B[a]P also led to decreased LSR and LDL-receptor protein, as well as modified LSR activity as lipoprotein receptor. We propose that dysregulation of lipid homeostasis in the liver may contribute towards B[a]P-induced weight gain in mice.