The association between Adenosine A_2A receptor gene polymorphisms and attention deficit hyperactivity disorder in Korean children

Attention deficit hyperactivity disorder (ADHD) is a common and heritable neurodevelopmental disorder. Particularly, ADHD is known to be related to the dopaminergic system. ADHD symptoms can appear when the dopamine binding affinity diminishes due to dopamine receptor abnormalities, such as the dopamine D₂ receptor (D₂R). This receptor interacts with the adenosine A_2A receptor (A_2AR). The A_2AR acts as an antagonist of D₂R, that is, the increased binding of adenosine with A_2AR inhibits the D₂R activity. Furthermore, it is found that the single nucleotide polymorphisms of the adenosine A_2A receptor gene (ADORA2A) revealed a significant relationship with ADHD in various populations. Therefore, we examined the genetic relationship between ADORA2A polymorphisms (rs2297838, rs5751876, and rs4822492) and Korean ADHD children. A case-control study was performed for 150 cases and 322 controls. Genotyping of ADORA2A polymorphisms was conducted by PCR-RFLP. The results demonstrated that the rs5751876 TC genotype was associated with children with ADHD (p = 0.018). The rs2298383 CC genotype was significantly associated with children with ADHD/HI (p = 0.026). However, when Bonferroni correction was used, the significance vanished (p_adjusted = 0.054 and p_adjusted = 0.078, respectively). Haplotype analysis showed that TTC, TCC, and CTG demonstrated a significant difference between ADHD/C children and control groups (p_adjusted = 0.006, p_adjusted = 0.011, and p_adjusted = 0.028, respectively). In conclusion, we propose a possible association between ADORA2A polymorphisms with Korean children having ADHD.