MOLECULAR ANALYSIS OF THE DOPAMINE TRANSPORTER IN ADHD

注意力缺陷/多动障碍(ADHD)是一种流行的 一种可能具有异质性病因的精神障碍 症状通常会持续到童年以后。既有熟悉度，又有 ADHD和ADHD症状的中等遗传度一直很好 这表明基因传播可能代表着一种 许多患有这种疾病的人的病因。这个 多巴胺转运体(DAT1=SLC 6a3)是一种候选易感基因 ADHD的基因，因为抑制多巴胺转运蛋白的药物 对某些症状的短期治疗是有效的 多动症。我们之前曾发现， 具有10个拷贝的可变数目串联重复(VNTR)等位基因 多巴胺转运蛋白基因座与ADHD在一个独立的样本中，我们 建议复制一个基于家庭的关联 125例三联体患者多巴胺转运体基因标记与ADHD的关系 由患有多动症的先证者和父母组成。诊断 ADHD将基于Kiddie-SADS-Lifetime版本(K-SADS- PL)。为了促进我们对这一现象的遗传学的理解 无序，先证者将在经历了一次 全面的诊断评估，以排除潜在的 令人困惑的效果。特别是，谁的孩子将被排除在外 ADHD可能是其他共病精神障碍的结果 (例如双相情感障碍的终生诊断)，疑似 ADHD的表观表现，或存在诊断不确定性的地方。 10拷贝等位基因在多巴胺转运体上的传递 轨迹将通过传递/不平衡检验进行分析， 带有特定假设的杂合子父母与10 此基因座上的复制等位基因和任何其他复制等位基因将 优先将10个拷贝等位基因传递给DSM-先证者 III-R诊断为ADHD。如果将连锁不平衡复制到 DSM-Rn-R诊断，DSM-IV亚型的连锁不平衡 ADHD将接受测试。如果之前的基于家庭的关联是 重复、持续筛选多巴胺转运蛋白基因 易感性突变，包括分子生物学研究 将支持越野车本身的安全。修改的标识 多巴胺转运蛋白基因座上的等位基因在 治疗红斑狼疮的改良药理药物的研究进展 ADHD，并可能协助设计和实施早期 遗传性疾病儿童的预防/干预策略 对多动症的易感性。

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder of presumably heterogeneous etiology whose symptoms often persist beyond childhood. Both the familiality of ADHD and the moderate heritability of ADHD symptoms have been well established, suggesting that genetic transmission may represent an etiological factor for many individuals with this disorder. The dopamine transporter (DAT1=SLC 6A3) is a candidate susceptibility gene for ADHD because drugs which inhibit the dopamine transporter are efficacious in the short-term treatment of some symptoms of ADHD. We have previously found linkage disequilibrium between a variable number tandem repeat (VNTR) allele with 10 Copies at the dopamine transporter locus and ADHD. In an independent sample, we propose to replicate the family-based association between a dopamine transporter genetic marker and ADHD in 125 trios consisting of an a proband with ADHD and both parents. Diagnosis of ADHD will be based upon the Kiddie-SADS-Lifetime Version (K-SADS- PL). In order to advance our understanding of the genetics of this disorder, probands will be selected after undergoing a comprehensive diagnostic evaluation to rule out potentially confounding effects. In particular, children will be excluded whose ADHD may be the result of other co-morbid psychiatric disorders (e.g. lifetime diagnosis of Bipolar Disorder), suspected phenocopies of ADHD, or where there is diagnostic uncertainty. Transmission of the 10 copy allele at the dopamine transporter locus will be analyzed by the transmission/disequilibrium test, with the specific hypothesis that heterozygous parents with the 10 copy allele and any other copy allele at this locus will preferentially transmit the 10 copy allele to probands with DSM- III-R diagnosed ADHD. If linkage disequilibrium is replicated with DSM-rn-R diagnosis, linkage disequilibrium in DSM-IV subtypes of ADHD will be tested. If the previous family-based association is replicated, continued screening of the dopamine transporter gene for susceptibility mutations, including molecular biological study of the VNTR itself will be supported. Identification of a modifying allele at the dopamine transporter locus would be useful in the development of improved pharmacological agents for treatment of ADHD and may assist in design and implementation of early prevention/intervention strategies for children with genetic susceptibility to ADHD.