Carrasco Ximena, Rothhammer Paula, Moraga Mauricio, Henríquez Hugo, Chakraborty Ranajit, Aboitiz Francisco, Rothhammer Francisco
Hospital Calvo Mackenna, Santiago, Chile.
Am J Med Genet B Neuropsychiatr Genet. 2006 Jan 5;141B(1):51-4. doi: 10.1002/ajmg.b.30259.
Attention-deficit/hyperactivity disorder, ADHD [MIM 126452], is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. As part of an ongoing study of ADHD, we carried out a family-based discordant sib-pair analysis to detect possible associations between dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms and ADHD in Chilean families. 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 (Fisher's exact test P > 0.25 in both cases). However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DAT1 10 allele homozygosity were significantly higher (34.6%) in cases (26), compared with their unaffected siblings (25) (4%; Fisher's exact test P = 0.0096; odds-ratio, OR = 12.71). Increased density of dopamine transporter 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 interaction worthy of further incisive studies.
注意缺陷多动障碍（ADHD）[MIM 126452]是一种常见的、具有高度遗传性的儿童期起病的神经生物学障碍，其特征为多动、冲动和/或注意力不集中。作为一项正在进行的ADHD研究的一部分，我们开展了基于家系的不一致同胞对分析，以检测智利家庭中多巴胺受体D4（DRD4）和多巴胺转运体1（DAT1）基因多态性与ADHD之间可能存在的关联。对于DRD4 7重复和DAT1 10重复等位基因，将两个位点分别分类为纯合子或杂合子，患病儿童与其健康同胞之间未表现出基因型频率差异（两种情况的Fisher精确检验P均>0.25）。然而，与未患病同胞（25人，占4%）相比，患病儿童（26人）中同时存在DRD4 7重复杂合性和DAT1 10等位基因纯合性的比例显著更高（34.6%）（Fisher精确检验P = 0.0096；优势比，OR = 12.71）。ADHD患者大脑中多巴胺转运体密度增加，以及前额叶皮质中7重复D4受体丰富，而ADHD患者的前额叶皮质受损，这使得观察到的基因-基因相互作用值得进一步深入研究。
