Kirley Aiveen, Hawi Ziarih, Daly Grainne, McCarron Mary, Mullins Celine, Millar Niamh, Waldman Irwin, Fitzgerald Michael, Gill Michael
Department of Genetics and Psychiatry, Trinity College, Dublin, Ireland.
Neuropsychopharmacology. 2002 Oct;27(4):607-19. doi: 10.1016/S0893-133X(02)00315-9.
Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of attention deficit hyperactivity disorder (ADHD). Several genetic association studies have been published, but so far, no DNA variants have been unequivocally demonstrated as contributing to ADHD susceptibility. Four dopamine related gene loci have been implicated, however: DAT 1, DRD 4, DBH, and DRD 5. Each of these may influence the liability of ADHD to a small degree. Notably, all are involved in signal transduction at the neuronal synapse. In this article, 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 article, we confirmed the previously reported association of DAT 1 (480 bp allele) with ADHD and identified polymorphisms at two additional loci showing preferential transmission to ADHD children of alleles at DRD 5 (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 of marginal significance. Nonsignificant trends of association were found for TH (allele 2) and DRD2 (Ser-311). No preferential transmission of alleles to ADHD children was observed for polymorphisms at DRD 1, DRD 2 (Taq I), DRD 3, DRD 4, and COMT. Analyzing the data by sex of transmitting parent showed significant preferential paternal transmission of alleles at TH (allele 2) and a nonsignificant trend for paternal transmission for DRD 2 (Ser-311). We attempt to put these findings together with what is known of the function of the particular proteins, and suggest working hypotheses.
越来越多的证据表明多巴胺神经传递异常与注意力缺陷多动障碍（ADHD）的病理机制有关。已经发表了几项基因关联研究，但到目前为止，尚未明确证明有DNA变异体导致ADHD易感性。然而，有四个与多巴胺相关的基因位点被牵连其中：DAT 1、DRD 4、DBH和DRD 5。这些基因中的每一个可能在一定程度上影响ADHD的易感性。值得注意的是，它们都参与神经元突触处的信号转导。在本文中，我们研究了多巴胺受体、多巴胺转运体以及已知参与多巴胺合成和代谢的基因的DNA多态性，将其作为ADHD的候选基因。在最近的一篇文章中，我们证实了先前报道的DAT 1（480 bp等位基因）与ADHD的关联，并在另外两个位点鉴定出多态性，显示DRD 5（148 bp等位基因）和DBH（等位基因2，Taq I多态性）的等位基因优先传递给ADHD儿童。还观察到多巴脱羧酶基因非翻译外显子1中4 bp缺失的传递增加，但意义不大。发现TH（等位基因2）和DRD2（Ser - 311）存在无显著意义的关联趋势。对于DRD 1、DRD 2（Taq I）、DRD 3、DRD 4和COMT的多态性，未观察到等位基因向ADHD儿童的优先传递。按传递亲本的性别分析数据显示，TH（等位基因2）存在显著的父系等位基因优先传递，DRD 2（Ser - 311）存在父系传递的无显著意义趋势。我们试图将这些发现与已知的特定蛋白质功能结合起来，并提出可行的假设。
