Augmented hyperaemia and reduced tissue injury in response to ischaemia in subjects with the 34C > T variant of the AMPD1 gene.
SourceEuropean Heart Journal, 28, 9, (2007), pp. 1085-91
Article / Letter to editor
Display more detailsDisplay less details
Epidemiology, Biostatistics & HTA
European Heart Journal
SubjectDCN 1: Perception and Action; DCN 2: Functional Neurogenomics; EBP 1: Determinants in Health and Disease; IGMD 3: Genomic disorders and inherited multi-system disorders; N4i 1: Pathogenesis and modulation of inflammation; NCEBP 14: Cardiovascular diseases; NCEBP 2: Evaluation of complex medical interventions; NCMLS 2: Immune Regulation; NCMLS 6: Genetics and epigenetic pathways of disease; ONCOL 3: Translational research; ONCOL 5: Aetiology, screening and detection; UMCN 1.5: Interventional oncology; UMCN 2.2: Vascular medicine and diabetes; UMCN 4.1: Microbial pathogenesis and host defense; UMCN 5.1: Genetic defects of metabolism
AIMS: In patients with coronary artery disease, the 34C > T variant of the adenosine mono-phosphate deaminase gene (AMPD1), encoding a dysfunctional protein, predicts improved survival. We hypothesized that in subjects with this variant allele, ischaemia-induced intracellular adenosine formation is increased, augmenting reactive hyperaemia and ischaemic tolerance. METHODS AND RESULTS: We selected 10 healthy subjects with the CT genotype and 10 CC controls. The forearm vasodilator response to 2 and 5 min of ischaemia (venous occlusion plethysmography, expressed as percentage of maximum blood flow after 13 min of ischaemia) was higher in the CT group 56% (49-74%) and 77% (71-86%) vs. 49% (42-53%) and 60% (55-70%) in the CC group [median (interquartile range), P = 0.01]. Additionally, ischaemia-reperfusion injury was assessed in the thenar muscle using (99m)Tc-annexin A5 scintigraphy after forearm ischaemic exercise to detect externalized membrane phosphatidylserines. At reperfusion, (99m)Tc-annexin was administered intravenously. The change in annexin targeting between 1 and 4 h post-injection was -2.3% (interquartile range -2.4 to -1.6%) in the CT group vs. -0.3% (-0.6 to 1.3%) in controls (n = 7 in both groups, P = 0.03). CONCLUSION: The 34C > T variant of AMPD1 augments vasodilation and reduces tissue injury in response to forearm ischaemia. These mechanisms could contribute to the survival benefit of cardiovascular patients with this variant allele.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.