Age- and gender-specific association between ADA (22G>A) and TNF-α (-308G>A) genetic polymorphisms

During the last years, several investigations have been performed to examine the influence of the tumor necrosis factor alpha (TNF-α) -308G>A single nucleotide polymorphism (SNP) in the susceptibility or severity of diseases and in many inflammatory conditions. However, the results of these studies have been conflicting, suggesting that, under normal/physiologic conditions, important disturbances in expression of major physiologic components can be compensated by mediators of the same system. In the present study, we evaluated the genetic relationship between the functional adenosine deaminase (ADA) (22G>A, rs73598374) and TNF-α (-308G>A, rs1800629) SNPs in a healthy population from central Italy. An association between ADA*2 and TNF-α*A was observed in males aged ≥ 50 [odds ratio (OR) = 5.16, P = 0.001]; a three-way contingency table analysis by a log-linear model shows a significant interaction between TNF-α genotype, ADA genotype, and age group (P = 0.012) for this gender. Overall, we may speculate that, in males, higher adenosine levels (conferred by ADA*2) may counteract the higher levels of TNF-α (conferred by TNF-α*A) in protective model of inheritance.