Combination of DRD4 and DAT1 genotypes is an important risk factor for attention deficit disorder with hyperactivity families living in Santiago, Chile

Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. Aim: To search for possible associations between dopamine receptor D4 (DRD4) and dopamine transporter 1(DAT1) polymorphisms and ADHD in Chilean families. Material and methods: We extended a previous family-based discordant sib pair analysis that included 26 cases diagnosed according to DSM-IV criteria and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls. Results: Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DAT1 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DAT1 10 allele homozygosity was significantly higher (22.5%) in cases (40), compared with (2.8%) unaffected siblings (36), with an odds-ratio of 10.16. Conclusions: The genotype combination DRD4/7 heterozygotes and DAT 1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interactions worthy of studies to understand the functional basis of ADHD