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Adenosine A2(A) receptor gene polymorphism (1976C>T) affects coronary flow reserve response during vasodilator stress

Maria Grazia Andreassi1, Franco Laghi Pasini, Eugenio Picano

  • 1CNR, Institute of Clinical Physiology, Pisa, Italy. john.stapleton@ucl.ac.uk

Pharmacogenetics and Genomics
|June 3, 2011
PubMed

Insights

Genetic variations in the A2(A) receptor gene, specifically the 1976C>T polymorphism, are linked to reduced coronary flow reserve in dilated cardiomyopathy patients. This finding impacts understanding of genetic influences on cardiac function during stress testing.

Area of Science:

  • Cardiology
  • Pharmacology
  • Genetics

Background:

  • Patients with non-ischemic dilated cardiomyopathy (DCM) exhibit an activated adenosinergic system and reduced coronary flow reserve (CFR).
  • Adenosinergic stress, induced by dipyridamole, is used to evaluate CFR via Doppler echocardiography.

Purpose of the Study:

  • To investigate the association between A2(A) receptor gene polymorphisms (263C>T and 1976C>T) and CFR response in DCM patients.
  • To explore the impact of these genetic variants on A2(A) receptor protein expression.

Main Methods:

  • Genotyping of A2(A) receptor polymorphisms (263C>T and 1976C>T) using polymerase chain reaction-restriction fragment length polymorphism analysis in 80 DCM patients and 162 controls.
  • Assessment of Doppler-derived CFR in DCM patients during dipyridamole-induced adenosinergic stress.
  • Evaluation of A2(A) receptor protein and mRNA expression in healthy controls.

Main Results:

  • No significant difference in genotype distribution for either polymorphism between DCM patients and controls.
  • Patients with the 1976TT genotype showed significantly lower CFR values compared to 1976CC patients.
  • Increased A2(A) receptor protein expression was observed in controls with the T1976 allele (heterozygous or homozygous).

Conclusions:

  • The A2(A) 1976C>T polymorphism is associated with a blunted coronary vasodilatory response in DCM patients.
  • This single nucleotide polymorphism appears to directly influence A2(A) receptor protein expression.
  • Further research is warranted to elucidate the functional role and clinical implications of this genetic variant in pharmacological stress cardiac imaging.
Abstract

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