Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.
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 A(1)-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.
Tang
Z
Z
Department of Medicine, The Center for Translational Medicine, The Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Diamond
M A
MA
Chen
J-M
JM
Holly
T A
TA
Bonow
R O
RO
Dasgupta
A
A
Hyslop
T
T
Purzycki
A
A
Wagner
J
J
McNamara
D M
DM
Kukulski
T
T
Wos
S
S
Velazquez
E J
EJ
Ardlie
K
K
Feldman
A M
AM
D020413:3' Untranslated Regions; D001483:Base Sequence; D009202:Cardiomyopathies / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D043682:Receptor, Adenosine A1 / Q000235:genetics*; D043705:Receptor, Adenosine A2A / Q000235:genetics; D043684:Receptor, Adenosine A3 / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D016277:Ventricular Function, Left / Q000235:genetics
D020413:3' Untranslated Regions; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3