The 22G>A polymorphism in the adenosine deaminase gene impairs catalytic function but does not affect reactive hyperaemia in humans in vivo.
OBJECTIVE
During ischaemia, the extracellular concentration of the endogenous nucleoside adenosine increases rapidly. Subsequent adenosine receptor stimulation induces various effects, including vasodilation, which can protect the tissue against the ischaemic insult. Adenosine deaminase (ADA) is an enzyme that catalyzes the irreversible deamination of adenosine. We hypothesized that the 22G>A polymorphism in the ADA gene inhibits its catalytic activity, and potentiates the protective effects of adenosine.


METHODS
In 96 healthy volunteers, blood was drawn to determine the ADA genotype, and the Vmax and Km values of the ADA from isolated erythrocytes. In a subgroup of volunteers (n=40) we measured the forearm vasodilator response to 13 min of forearm ischaemia using venous occlusion plethysmography as a read-out parameter for adenosine receptor stimulation.


RESULTS
Although healthy volunteers with the 22GA genotype had a lower Vmax value of ADA than volunteers with the GG genotype (61.6+/-4.3 ng/min/mg, n=14, vs. 78.0+/-2.8 ng/min/mg, n=82; P=0.02), this did not potentiate the forearm vasodilator response to 13 min of ischaemia (77.4+/-8.8 ml/dl in the GA group (n=5) vs. 87.0+/-5.0 ml/dl (n=35), area under the curve, P=0.3).


CONCLUSIONS
We conclude that heterozygosity for the 22G>A variant of ADA, although reducing catalytic activity, does not enhance forearm reactive hyperaemia. Therefore, the 22G>A variant probably does not contribute to any variability in the protective cardiovascular effects of adenosine.
Riksen
Niels P
NP
Departments of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Franke
Barbara
B
van den Broek
Petra
P
Naber
Marlies
M
Smits
Paul
P
Rongen
Gerard A
GA
D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000235:genetics*; D000328:Adult; D002384:Catalysis; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D005542:Forearm; D005838:Genotype; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy / Q000235:genetics*; D007700:Kinetics; D008297:Male; D011110:Polymorphism, Genetic; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000243:Adenosine Deaminase; D000241:Adenosine