A promoter polymorphism (-839 C > T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children.

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission and is also the major site of action for methylphenidate which is one of the main drugs used to treat attention deficit hyperactivity disorder (ADHD). Most association studies with ADHD have concentrated on the 3'-untranslated region of the gene (3'-UTR) mainly in a variable number of tandem repeat (VNTR) polymorphism, but these investigations have reported discordant results. In this study, we tested this VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using family-based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D' = 0.56; P = 0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P = 0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P = 0.004). Our results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample.