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. 1085-1091
Article / Letter to editor
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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.
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