Assessment of triglyceride clearance in a FH population with variations in heparan sulfate biosynthesis.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Triglyceride clearance
Secondary outcome
LPL binding capacity
Urine albumin and glycosaminoglycan profile
Background summary
Hypertriglyceridemia is an independent risk factor for cardiovascular disease
and can be caused by decreased clearance of triglyceride-rich
lipoproteins(TRLs) in the liver. In this protocol we will focus on a recently
discovered pathway in which TRLs are cleared through heparan sulfate
proteoglycans (HSPGs)-assisted endocytosis in the liver. Animal research has
elucidated many of the steps in this process but human relevance still remains
to be determined. Our hypothesis is that HSPGs are instrumental in the removal
of TRLs from the circulation in humans. We hypothesize that HSPGs are
instrumental in the clearance of TRLs from the circulation in humans. An
important gene in this proces, NDST, codes for N-deacetylase/
N-sulfotransferase, which determines sulfation of heparan sulfate, a
glycosaminoglycan that is present throughout the human body. Patients with FH
have a mutation in the LDL receptor, and therefore can clear the TRLs less
well. Because clearance in this situation is more dependent on HSPGs, genetic
variation might result in clearance variation. We would like to investigate
whether individuals with a decrease in HSPG sulfation show a decrease
triglyceride clearance.
Study objective
Assessment of triglyceride clearance in a FH population with variations in
heparan sulfate biosynthesis.
Study design
In the current study we want to evaluate the triglyceride clearance in a
population of FH individuals characterized by the NDST tag SNP:
TT (10 individuals wildtype)
GT (10 individuals heterozygous allele)
GG( 10 individuals homozygous allele)
* Oral fat loading test (OFLT) to investigate lipid clearance
* LPL test to determine LPL binding
* Standard CV risk biochemistry panel(incl. Cholesterol/crp/hba1c). Also
plasma/urine samples for determination of total glycosaminoglycan
concentration/sulfation.
Intervention
1. Fat loading test with subsequent blooddrawing
2. LPL-test using heparin
Study burden and risks
Fat loading test is a routine test in our department which requires repetitive
blood sampling from an indwelling venous catheter after the consumption of
cream and Vitamin A. The low dose of heparin used for the LPL test will not
cause any side effects. We believe the information gathered from this study
outweighs the burden of these interventions.
Meibergdreef 9
1105 az
NL
Meibergdreef 9
1105 az
NL
Listed location countries
Age
Inclusion criteria
Heterozygous mutation in LDL receptor (heterozygous Familial Hypercholesterolemia)
Exclusion criteria
diabetes
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL31380.018.10 |