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Adenosine A2(A) receptor gene polymorphism (1976C>T) affects coronary flow reserve response during vasodilator stress testing in patients with non ischemic-dilated cardiomyopathy.

Author(s): Andreassi MG, Laghi Pasini F, Picano E, Capecchi PL, Pompella G, Foffa I, Borghini A, Sicari R

Affiliation(s): CNR, Institute of Clinical Physiology, Pisa, Italy. john.stapleton@ucl.ac.uk

Publication date & source: 2011-08, Pharmacogenet Genomics., 21(8):469-75.

Publication type: Randomized Controlled Trial

OBJECTIVES: Patients with non ischemic-dilated cardiomyopathy (DCM) are characterized by an activation of the adenosinergic system and reduced coronary flow reserve (CFR) evaluated by transthoracic Doppler echocardiography during vasodilator adenosinergic stress (dipyridamole administration). The aim of this study was to assess whether genetic polymorphisms (263C>T and 1976C>T) of the A2(A) receptor gene affect CFR response in patients with DCM. METHODS: We enrolled a group of 80 patients with DCM (55 male; age, 62+/-10.3 years) and 162 healthy volunteers (55 male; age, 45.1+/-9.5 years). Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was determined in DCM. A2(A) receptor genotyping was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism analysis. The expression of A2(A) protein and mRNA was also assessed in healthy controls. RESULTS: The genotype distribution of the 263C>T (P=0.5) and 1976C>T (P=0.8) polymorphisms was not significantly different between patients and controls. Patients with 1976TT genotype had significantly lower CFR value than 1976CC patients (2.3+/-0.7, 2.0+/-0.5 and 1.9+/-0.4, P<0.05 for CC, CT and TT genotypes, respectively). Controls who were heterozygous (P=0.02) or homozygous (P=0.001) for the T1976 allele showed a significant increase in A2(A) receptor protein. CONCLUSION: These data demonstrate that A2(A) 1976C>T polymorphism is associated with a blunted coronary vasodilatory response in patients with DCM, and support a direct consequences of this single nucleotide polymorphism for protein expression. Additional studies are needed to better define the functional role of this genetic variant as well as to clarify the potential clinical impact of genetics during pharmacological stress cardiac imaging.

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