Augmented hyperaemia and reduced tissue injury in response to ischaemia in subjects with the 34C > T variant of the AMPD1 gene

• Published in: European heart journal Vol. 28; no. 9; pp. 1085 - 1091
• Main Authors: Riksen, Niels P., Franke, Barbara, Oyen, Wim J.G., Borm, George F., van den Broek, Petra, Boerman, Otto C., Smits, Paul, Rongen, Gerard A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2007; Oxford Publishing Limited (England)
• Subjects: Adult; AMP Deaminase - genetics; Biological and medical sciences; Cardiology. Vascular system; Dipyridamole - pharmacology; Female; Forearm - blood supply; Humans; Hyperemia - genetics; Ligation; Male; Medical sciences; Reperfusion Injury - genetics; Vasodilator Agents - pharmacology; Ischaemia; Adenosine; Scintigraphy; genotype; Blood flow; Radionuclide study; Human; Typing; Injury; AMPD1 genotype; Cardiovascular disease; Genotype; Phlebology; Trauma; Response; Variant; Tissue; Microbiological investigation; Gene; Ischemia; Medical imagery; Genetics; Circulatory system; Lesion; Cardiology
• DOI: 10.1093/eurheartj/ehm032
• ISSN: 0195-668X

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 99mTc-annexin A5 scintigraphy after forearm ischaemic exercise to detect externalized membrane phosphatidylserines. At reperfusion, 99mTc-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.