Ondezoek naar de aanmaak en afbraak van cholesterolvetdeeltjes in patiënten met familiaire hypercholesterolemie

Familial hypercholesterolemia (FH) is characterized by increased low density lipoprotein (LDL) cholesterol and increased cardiovascular risk. There are 3 known genes (LDLR, ApoB, PCSK9) in which mutations can lead to the FH phenotype (FH1 to 3 respectively). However, in approximately 5-10% of patients such a mutation cannot be found, despite family-based linkage studies (the so called FH4 group). Therefore, a more elaborate approach is deemed necessary, where data derived from transcriptome, proteome, and metabolome studies are combined to find novel genes and metabolic pathways in lipid metabolism. We aim to acquire in depth phenotyping in selected FH4 patients by extensive lipoprotein kinetic flux studies yielding insights into the pathophysiological mechanism of FH4. To study “in vivo” apolipoprotein B100 and cholesterol metabolism in patients with FH4, and to compare the results with healthy family controls and dyslipidemic patients with mutations in established lipid genes(i.e. FH1 – FH3). This will ultimately help to answer the fundamental question as to whether FH4 is a result of overproduction or a decreased catabolism of ApoB containing lipoproteins.

Familial hypercholesterolemia of unknown origin (FH4) is caused by an overproduction or a decreased catabolism of ApoB containing lipoproteins

Visit 1: all patients

Visit 2: (optional) after discontinuation of lipid lowering therapies for 4 weeks

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