1. ¹Department of Medicine, The Center for Translational Medicine, The Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
2. ²INSERM U613, Brest, France
3. ³Etablisement Français du Sang—Bretagne, Brest, France
4. ⁴Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
5. ⁵Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
6. ⁶First Department of Cardiology, Silesian Center for Heart Diseases, Silesian Medical School, Zabrze, Poland
7. ⁷Second Department of Cardiac Surgery, Medical University of Silesia, Katowice, Poland
8. ⁸Division of Cardiovascular Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
9. ⁹Genomics Collaborative Inc., Cambridge, Massachusetts, USA

Correspondence: AM Feldman, (arthur.feldman@jefferson.edu)

Received 20 June 2007; Accepted 5 July 2007; Published online 29 August 2007.

Abstract

The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A₁-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.