Blood Flow in Healthy Volunteers Clinical Trial
Official title:
The Influence of the 1976T>C Polymorphism in the Adenosine A2A Receptor Gene on Adenosine-Induced Vasodilation and the Influence of the 34C>T Polymorphism in the AMP Deaminase Gene on Post-Occlusive Reactive Hyperemia.
The endogenous nucleoside adenosine can induce various cardiovascular and neurohumoral effects by stimulation of specific adenosine receptors. taken together these effects protect against ischaemia-reperfusion injury of (myocardial)muscles and agsinst the development of atherosclerosis. Genetic variations in genes encoding for adenosine receptors or for enzymes involved in the formation or breakdown of adenosine could potentially modulate these effects. In this study, we aim to determine the functional effects of two frequent genetic polymorphisms in the adenosine receptor and AMPdeaminase (involved in the formation of adenosine) on the vascular effects of adenosine.
The endogenous nucleoside adenosine can induce various cardiovascular and neurohumoral
effects by stimulation of specific adenosine receptors. taken together these effects protect
against ischaemia-reperfusion injury of (myocardial)muscles and agsinst the development of
atherosclerosis. Genetic variations in genes encoding for adenosine receptors or for enzymes
involved in the formation or breakdown of adenosine could potentially modulate these
effects. In this study, we aim to determine the functional effects of two frequent genetic
polymorphisms in the adenosine receptor and AMPdeaminase (involved in the formation of
adenosine) on the vascular effects of adenosine.
In 100 healthy young volunteers, we will determine the genotype of the adenosine A2A
receptor gene. We expect to find approximately 15 subjects with the 1976T>C polymorphisms.
It is known that this polymorphism is associated with an increased neuropsychological
sensitivity to caffeine administration.
We will explore whether this polymorphism is associated with a different vasodilating
response to the administration of adenosine and caffeine into the brachial artery. Blood
flow will be measured with venous occlucion plethysmography.
Secondly, we will also determine the genotype of the AMPD1 gene. We expect to find 15
subjects with the 34C>T mutation, which is a loss-of-function-mutation. Cardiovascular
patients with this mutation are known to have a survival benefit. We will explore whether
the post-occlusive reactive hyperemia in the forearm is potentiated, because during
ischaemia, more adenosine is formed in these subjects.
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Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Diagnostic