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…
ID
Bron
Verkorte titel
Aandoening
Familial hypercholesterolemia
Genetics
Cholesterol
LDL
Familiaire hypercholesterolemie
Genetica
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
- SNP’s and DNA methylation percentage will be analysed using a multivariable linear regression analyses.<br>
- RNA sequencing and gene expression will be expressed relative to controls, and in a subgroup with and without LLT.<br>
- Protein and lipid content measured through mass spectrometry will be expressed as relative abundance in subjects (on and off LLT) and controls. Heatmaps will be used to display relative differences between groups.<br>
- Protein assessed with ELISA assays will be expressed as means and compared with a student’s t-test.<br>
- Fast protein liquid chromatography (FPLC) on lipoprotein cholesterol levels will be expressed as means and compared with a student’s t-test.
Achtergrond van het onderzoek
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. In this study we will combine data derived from the genome, epigenome, transcriptome, proteome, and metabolome to find novel genes and metabolic pathways in lipid metabolism.
Doel van het onderzoek
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 the genome, epigenome, transcriptome, proteome, and metabolome are combined to find novel genes and metabolic pathways in lipid metabolism.
Onderzoeksopzet
Visit 1: under lipid lowering therapy
Visit 2: after discontinuation of lipid lowering therapy for 4 weeks
Onderzoeksproduct en/of interventie
none
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- Diagnosis of familial hypercholesterolemia based on Dutch Lipid Clinic Network criteria (Nordestgaard et al. 2013) in combination with a negative DNA-testing (mutations in LDLR, ApoB, PCSK9).
- Untreated LDL-cholesterol levels of > 95th percentile for age and gender
- >18 years of age
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
Abusive alcohol use
Dysthyroidism
Pregnancy, breastfeeding
Diabetes mellitus
Use of medication that might elevate lipid levels
Opzet
Deelname
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Andere (mogelijk minder actuele) registraties in dit register
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL6881 |
| NTR-old | NTR7059 |
| CCMO | NL62407.018.17 |
| OMON | NL-OMON44591 |