Clinical trial NCT00253929: Effect of Polymorphisms in the Adenosine a2a Receptor Gene and AMPD2 Gene on Adenosine-Induced Vasodilation and Reactive Hyperemia
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Flow in Healthy Volunteers
Keywords: adenosine
polymorphisms
blood flow
adenosine A2a receptor
AMP deaminase
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2005-11-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 18-40 year

Exclusion Criteria:

* hypertension
* diabetes
* cardiovascular or pulmonary disease
* asthma

Primary outcomes:
measure: A2A: adenosine- and caffeine induced vasomotion (blood flow)
measure: AMPD:post-occlusive reactibe hyperemic blood flow
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Gerard Rongen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Paul Smits, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Riksen NP, Franke B, van den Broek P, Naber M, Smits P, Rongen GA. The 22G>A polymorphism in the adenosine deaminase gene impairs catalytic function but does not affect reactive hyperaemia in humans in vivo. Pharmacogenet Genomics. 2008 Oct;18(10):843-6. doi: 10.1097/FPC.0b013e328305e630.