Genetic lipid disorders, the APOE gene and Familial Dysbetalipoproteinemia

Abstract

One of the most important risk factors for cardiovascular disease (CVD) is dyslipidemia. Dyslipidemia is caused by lifestyle factors and by genetic predisposition. Although the focus in research has been on low-density lipoprotein-cholesterol (LDL-C), dyslipidemia involves the metabolism of many more lipids and lipoproteins, and any imbalance in this metabolism can potentially lead to atherosclerosis and CVD. Familial Dysbetalipoproteinemia is a genetic lipid disorder and associated with increased CVD risk. In this thesis the relationship between genes, lipoproteins and CVD was investigated, with a focus on FD. The first part of this thesis focuses on the risk of (genetic susceptibility) of increased lipid levels on the risk of (recurrent) vascular events. The second part describes different aspects of FD. Risk factors for the development of FD were evaluated and approaches to establish the relationship between FD and genetic variants in the APOE gene were proposed. Furthermore, a randomized trial was conducted to study the effects of the PCSK9 monoclonal antibody evolocumab on fasting and post fat lipid levels in patients with FD.