To define the role of genetic variations in SNARE protein genes in the regulation of VWF plasma concentrations and their effect on other substances secreted by WPBs and alpha-granules and coagulation parameters under physiological circumstances.
ID
Source
Brief title
Condition
- Coagulopathies and bleeding diatheses (excl thrombocytopenic)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The VWF plasma concentration will change after heavy exercise and this change
will differ among genotypes. We expect a 60% increase of VWF plasma levels
after heavy exercise and approximately 30% difference between genotypes.
Secondary outcome
Other coagulation parameters and substances secreted by WPBs.
To what extent does variation in skin-autofluorescence as a non-invasive marker
for accumulation of advanced glycation endproducts and atherosclerotic
processes explain the variance in the regulation of VWF concentration?
Background summary
High VWF levels have been associated with an increased risk of CVD. However,
factors which are involved in the regulation of VWF plasma concentrations are
largely unknown. Recently, a meta-analysis of genome-wide association studies
of the CHARGE consortium revealed two novel genes, STXBP5 and STX2, which are
highly associated with VWF levels. These genes encode proteins, which are
involved in the regulation of numerous secretory events, such as Weibel Palade
Body (WPB) exocytosis. WPBs and alpha-granules release large amounts of VWF
upon endothelial cell activation, as in atherosclerosis and subsequent arterial
thrombosis. In addition, these storage granules do not only secrete VWF
molecules, but also other pro-inflammatory factors and pro-thrombotic factors.
It is yet unknown how SNARE proteins exactly regulate VWF plasma concentration
and how SNARE proteins contribute possibly to the occurrence of arterial
thrombosis.
Study objective
To define the role of genetic variations in SNARE protein genes in the
regulation of VWF plasma concentrations and their effect on other substances
secreted by WPBs and alpha-granules and coagulation parameters under
physiological circumstances.
Study design
We will perform an observational study among 100 healthy volunteers, males and
females, aged 18-35 years. During an inclusion period of 8 months we will
recruit healthy volunteers (student and employees of the Erasmus MC) via
advertisements in the Erasmus University Medical Center building and in the
local Erasmus magazine.
During the clinic visit a short interview will be taken, as well as a physical
examination, including blood pressure, height, and weight measurements. Blood
will be drawn before and after the cycle ergometer test. Study participants
will perform a cycle ergometer test during approximately 20 minutes. The
subject will start with a warming-up of 4 minutes. Every 6 seconds the cycling
resistance will increase by 2 watt until exhaustion. Subsequently, resistance
will decrease again and the participant can cool down for five minutes. During
the cycle ergometer test the heart rhythm will be monitored continuously with
ECG and VO2 will be measured.
Fore-arm skin autofluorescence will be measured using the AGE-reader®.15 The
measurement is completely automated and is obtained by placing the forearm on
the device. The measurement takes aproximately 1 min to complete.
Study burden and risks
Participants will visit the once. A short interview will consist of health
related questions. The physical examination includes blood pressure, height,
and weight measurements. At two different time points a total of 45 mL. blood
will be collected from each participant. The blood sampling may cause a
haematoma or minor bleeding. Participants will perform considerable physical
exercise during 20 minutes. By selecting only healthy volunteers and by
continuously monitoring heart rhythm with ECG and measuring the VO2, there are
no risks associated with this intervention.
There are now risks associated with the AGE-reader measurement.
's Gravendijkwal 230, kamer L-435
3015 CE Rotterdam
NL
's Gravendijkwal 230, kamer L-435
3015 CE Rotterdam
NL
Listed location countries
Age
Inclusion criteria
- Males and females
- 18 - 35 years
- Caucasians
Exclusion criteria
- Known cardiovascular risk factors, such as hypertension, diabetes,
hypercholesterolemia, obesity (BMI > 30 kg/m2), and a positive family history of CVD.
- Smoking
- Use of medication known to influence VWF levels, such as statins, beta-blockers etc.
(oral contraceptive use is allowed).
- Known malignancies, liver dysfunction or renal dysfunction.
- Pregnancy
- If the participant wishes not to be informed about clinically relevant abnormalities that could be detected during the study.
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 | NL32877.078.10 |