Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of ADHD. Several genetic association studies have been published but so far, no DNA variants have been unequivocally demonstrated as contributing to ADHD susceptibility. However 5 dopamine related gene loci have been implicated; DAT1, DRD4, DBH, DRD5 and COMT. Each of these may influence the liability of ADHD to a small degree. Notably all are involved in signal transduction at the neuronal synapse. We investigate as candidate genes for ADHD, DNA polymorphisms at dopamine receptors, the dopamine transporter, and genes known to be involved in dopamine synthesis and metabolism. In a recent paper, we confirmed the previously reported association of DAT1 (480 bp allele) with ADHD and identified polymorphisms at two additional loci showing preferential transmission to ADHD children of alleles at DRD5 (148 bp allele) and at DBH (allele 2, Taq I polymorphism). Increased transmission of the 4 bp deletion in the untranslated exon 1 of the DOPA decarboxylase gene was also observed but was not significant at P <0.05. No preferential transmission of alleles to ADHD children was observed for polymorphisms at DRD1, DRD2, DRD3, DRD4, COMT and TH. Analysing the data by sex of transmitting parent showed a greater relative risk for paternal transmission of the DAT1 480 bp allele and significant excess transmission of paternal alleles at TH (allele 2) and DRD2 (Ser-311). We attempt to put these findings together with what is known of the function of the particular proteins, and suggest working hypotheses.
|Number of pages
|American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
|Published - 8 Oct 2001