Coronary artery disease. A study of three polymorphic sites of adenosine deaminase gene.

ABSTRACT

OBJECTIVES: The role of adenosine as a cardioprotective agent is well known and recent experimental studies suggest that impairment of adenosine-related signal transduction contributes to the pathophysiology of chronic heart failure. The recent observation of an association between ADA, genetic polymorphism and coronary artery disease (CAD) prompted us to study the possible relevance of three intragenic polymorphic sites of the ADA gene (ADA1, ADA2 and ADA6). METHODS AND RESULTS: 136 non-diabetic patients with coronary artery disease and 246 healthy blood donors from the white Italian population of Central Italy and 129 non-diabetic patients with CAD and 204 newborns from the white Polish population were studied. ADA1, ADA2 and ADA6 genotypes were determined by DNA analysis. In males, the proportion of ADA1 *2 (P = 0.0001) and ADA2 *2 (P = 0.005) alleles is lower in CAD than in controls. In males, the haplotype distribution of the pairs ADA1-ADA2, ADA1-ADA6 and ADA2-ADA6 shows statistically significant differences between coronary artery disease and controls. CONCLUSIONS: The present study suggests a complex association between ADA gene and coronary artery diseases. Besides the control of adenosine concentration due to deamination of adenosine, also other functions of the ADA gene could have a role in the susceptibility and/ or clinical course of coronary artery disease.