title: Adenosine A2(A) receptor gene polymorphism (1976C>T) affects coronary flow reserve response during vasodilator stress testing in patients with non ischemic-dilated cardiomyopathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy. john.stapleton@ucl.ac.uk
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi Pasini
authors.forename: Eugenio
authors.initials: E
authors.lastname: Picano
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Gerarda
authors.initials: G
authors.lastname: Pompella
authors.forename: Ilenia
authors.initials: I
authors.lastname: Foffa
authors.forename: Andrea
authors.initials: A
authors.lastname: Borghini
authors.forename: Rosa
authors.initials: R
authors.lastname: Sicari
mesh_terms: D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging*; D003326:Coronary Circulation / Q000187:drug effects / Q000235:genetics*; D004176:Dipyridamole; D015150:Echocardiography, Doppler; D005080:Exercise Test; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043683:Receptors, Adenosine A2 / Q000235:genetics*; D014665:Vasodilator Agents
chemical_list: D043683:Receptors, Adenosine A2; D014665:Vasodilator Agents; D004176:Dipyridamole