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The Influence of the 34C>T Variant in the AMPD1 Gene Ischemic Tolerance

2014-08-27 03:45:02 | BioPortfolio

Summary

Previous epidemiological studies have shown that in cardiovascular patients, the 34C>T variant in the gene encoding for the enzyme Adenosine Mono Phosphate Deaminase (AMPD1) is associated with prolonged survival.

The 34 C>T variant encodes a severely truncated, metabolically inactive protein. We hypothesize that during ischemia, in these patients AMP in preferentially converted into adenosine instead of IMP. Adenosine receptor stimulation, in turn, will increase resistance to ischemia-reperfusion in the myocardial tissue.

To test this hypothesis, 7 male healthy volunteers heterozygous for the 34C>T variant will be selected from 100 healthy volunteers, which we have previously genotyped. These subjects will be compared with 7 matched control subjects. Individual ischemic tolerance will be assessed in the thenar muscle using 99mTc-Annexin A5 scintigraphy.

Briefly, the circulation of the nondominant forearm will be interrupted for 10 minutes by inflation of an upperarm cuff to 200mmHg en concomitantly, the subjects will perform isometric rhythmic handgripping until exhaustion. Immediately upon reperfusion, 400 MBq of 99mTc-Annexin A5 will be administered intravenously. Finally, 1 and 4 hours post-injection, scintigrapghi imaging of both hand will be performed. Targeting of annexin A5 will be expressed as percentage difference between the experimental and control hand.

Study Design

Allocation: Non-Randomized, Control: Placebo Control, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Diagnostic

Conditions

AMPD

Intervention

systemic administration of 99mTc-HYNIC-Annexin A5, 10 minutes of ischemic handgripping

Status

Active, not recruiting

Source

Radboud University

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:45:02-0400

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Medical and Biotech [MESH] Definitions

A member of the annexin family that is a substrate for a tyrosine kinase, ONCOGENE PROTEIN PP60(V-SRC). Annexin A2 occurs as a 36-KDa monomer and in a 90-KDa complex containing two subunits of annexin A2 and two subunits of S100 FAMILY PROTEIN P11. The monomeric form of annexin A2 was formerly referred to as calpactin I heavy chain.

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Protein of the annexin family exhibiting lipid interaction and steroid-inducibility.

Protein of the annexin family with a probable role in exocytotic and endocytotic membrane events.

An annexin family member that plays a role in MEMBRANE FUSION and signaling via VOLTAGE-DEPENDENT CALCIUM CHANNELS.

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