APOE gene variants in primary dyslipidemia

Abstract

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.

Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses

“…These isoforms differ considerably in terms of their receptor-binding or functional activities. Indeed, ApoE2 (cys112, cys158) has been reported to be defective for receptor binding and has been implicated in several diseases, including type III hyperlipoproteinemia [ 11 ]. ApoE4 (arg112, arg158) has low molecular stability, which influences its ability to bind lipoproteins, and has been implicated in the development of atherosclerosis and neurological disorders.…”

Familial Hypercholesterolemia: Real-World Data of 1236 Patients Attending a Czech Lipid Clinic. A Retrospective Analysis of Experience in More than 50 years. Part I: Genetics and Biochemical Parameters

“…To the best of our knowledge, no mutation in the PCSK9 gene in the Czech population has been reported to date. An important role is also played by the apolipoprotein E ( APOE ) gene, which affects the levels of LDL-C thus contributing to higher LDL-C levels in FH patients ( Pirillo et al, 2017 ; Rashidi et al, 2017 ; Khalil et al, 2021 ).…”

Association of DNA methylation and genetic variations of the APOE gene with the risk of diabetic dyslipidemia

“…In addition, a review study reported that the common and rare APOE variants alongside environmental factors and epigenetics are associated with variations in lipids and lipoprotein levels affecting the clinical presentation of dyslipidemia (39). Together, these results indicated that molecular screening of the APOE gene and study of epigenetic variations are crucial to understanding the implications of the APOE variants in each of these diseases, which would be possible using high throughput sequencing, i.e NGS.…”