To unravel the cause(s) of the FH phenotype in patients with no mutations in well-established lipid genes (LDLR, APOB, PCSK9).
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are novel mutations/SNP*s associated with
hypercholesterolemia, methylation of target genes, DNA expression,
(semi-)quantification of proteins (proteomics), (semi-)quantification of
metabolites (e.g. lipids/fatty acids) in FH4 patients compared with matched
controls
Secondary outcome
nvt
Background summary
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.
Study objective
To unravel the cause(s) of the FH phenotype in patients with no mutations in
well-established lipid genes (LDLR, APOB, PCSK9).
Study design
Matched case-control study.
Study burden and risks
Patients will be subjected to venous blood sampling (60 ml total). A subgroup
of FH4 cases, those on lipid lowering therapy for primary prevention, might be
asked to participate again after a washout period of 4 weeks of those
medication. This will result in temporarily higher LDL-C levels, mildly
increasing the risk for CVD. However, we think that this additional risk is
minimal in the light of a life time exposure to high LDL-C levels in FH4
patients.
Meibergdreef 9
Amsterdam-Zuidoost 1105AZ
NL
Meibergdreef 9
Amsterdam-Zuidoost 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- 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, or between 20-60th percentile for family controls
- >18 years of age
Exclusion criteria
- Heavy alcohol use
- Dysthyroidism
- Renal insufficiency (creatinine >150 µmol/L)
- Diabetes mellitus
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL62407.018.17 |
| OMON | NL-OMON27045 |