Contributors: Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord; Université Paris Cité (UPCité); Université Saint-Joseph de Beyrouth (USJ); Hôpital Ambroise Paré AP-HP; Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ); 13CVD03 Agence Nationale de la Recherche, ANR: ANR-16-RHUS-0007 Fondation Leducq Institut National de la Santé et de la Recherche Médicale, Inserm Conseil National de la Recherche Scientifique, CNRS-L; YAK is supported by a grant from Ministère de l’Education Nationale et de la Technologie (France) , a grant from Nouvelle Société Francophone de l’Athérosclérose (France) , and a grant from Lebanese National Council for Scientifc Research (CNRS-L) .; This work was supported by grants from Leducq Foundation (FLQ # 13CVD03), The national project CHOPIN (CHolesterol Personalized Innovation) granted by the National Research Agency (ANR-16-RHUS-0007), INSERM (Institut National de la Sant? et de la Recherche M?dicale), Conseil de la recherche of Saint-Joseph University of Beirut, and CEDRE program.YAK is supported by a grant from Minist?re de l'Education Nationale et de la Technologie (France), a grant from Nouvelle Soci?t? Francophone de l'Ath?roscl?rose (France), and a grant from Lebanese National Council for Scientifc Research (CNRS-L).; This work was supported by grants from Leducq Foundation ( FLQ # 13CVD03 ), The national project CHOPIN (CHolesterol Personalized Innovation) granted by the National Research Agency ( ANR-16-RHUS-0007 ), INSERM (Institut National de la Santé et de la Recherche Médicale) , Conseil de la recherche of Saint-Joseph University of Beirut , and CEDRE program .; ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016)
نبذة مختصرة : International audience ; Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations in lipid and lipoprotein levels and thus cardiovascular risk. The isoform apoE4 is associated with an increase in LDL-cholesterol levels and thus a higher cardiovascular risk compared to apoE3. Whereas, apoE2 is associated with a mild decrease in LDL-cholesterol levels. In the presence of other risk factors, apoE2 homozygotes could develop type III hyperlipoproteinemia (familial dysbetalipoproteinemia or FD), an atherogenic disorder characterized by an accumulation of remnants of triglyceride-rich lipoproteins. Several rare APOE gene variants were reported in different types of dyslipidemias including FD, familial combined hyperlipidemia (FCH), lipoprotein glomerulopathy and bona fide autosomal dominant hypercholesterolemia (ADH). ADH is characterized by elevated LDL-cholesterol levels leading to coronary heart disease, and due to molecular alterations in three main genes: LDLR, APOB and PCSK9. The identification of the APOE-p.Leu167del variant as the causative molecular element in two different ADH families, paved the way to considering APOE as a candidate gene for ADH. Due to non mendelian interacting factors, common genetic and environmental factors and perhaps epigenetics, clinical presentation of lipid disorders associated with APOE variants often strongly overlap. More studies are needed to determine the spectrum of APOE implication in each of the diseases, notably ADH, in order to improve clinical and genetic diagnosis, prognosis and patient management. The purpose of this review is to comment on these APOE variants and on the molecular and clinical overlaps between dyslipidemias.
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