Smoking and hypertension: Effect of adenosine deaminase polymorphism

Adenosine modulates cardiovascular functions reducing blood pressure and heart rate. Adenosine deaminase (ADA) by the irreversible deamination of adenosine to inosine contributes to the regulation of adenosine concentration in body fluids. We have studied the interaction between smoking and ADA genetic variability concerning their effects on blood pressure. We have studied 344 subjects admitted to the hospital for cardiovascular diseases. The genotypes of two polymorphic loci within the ADA gene were determined: ADA(1) and ADA(2). Both loci show two alleles: ADA(1)*1 and ADA(1)*2 in ADA(1) locus and ADA(2)*1 and ADA(2)*2 in ADA(2) locus. In the absence of smoking, the proportion of subjects with hypertension tends to be lower in carriers of the ADA(1)*2 allele. In smoking subjects, the pattern is reversed and the proportion of those with hypertension tends to be higher in carriers of the ADA(1)*2 allele. A similar pattern is observed for ADA(2) locus. Smoking increases the proportion of subjects showing hypertension: such effect is more marked in those carrying the ADA(1)*2 allele as compared to subjects with ADA(1)*1/*1 genotype. The same pattern of association is observed for ADA(2) locus. The two loci show an additive effect. The odds ratio for hypertension in smokers vs nonsmokers is 1.450 in subjects carrying ADA(1)*1/*1 and ADA(2)*1/*1 genotypes, while it is 11.200 in subjects carrying the *2 alleles in both loci. From a practical point, a view of our results suggest that smokers carrying both ADA(1)*2 and ADA(2)*2 alleles have a higher risk of hypertension.