McCracken J T, Smalley S L, McGough J J, Crawford L, Del'Homme M, Cantor R M, Liu A, Nelson S F
Department of Psychiatry and Biobehavioral Scienes, UCLA Neuropsychiatric Institute, Mental Retardation Research Center, UCLA School of Medicine, Los Angeles, CA 90024-1759, USA.
Mol Psychiatry. 2000 Sep;5(5):531-6. doi: 10.1038/sj.mp.4000770.
Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder. Evidence from twin, adoption, and family studies provide support for a genetic contribution to the etiology of ADHD. Several candidate gene studies have identified an association between a 7-repeat variant in exon 3 of the dopamine 4 receptor gene (DRD4) and ADHD. However, in spite of the positive reports finding association of the exon 3 VNTR with ADHD, several other polymorphisms within DRD4 have been identified that conceivably could contribute to risk for ADHD. Recently, another common polymorphism of the DRD4 gene has been described involving a 120-bp repeat element upstream of the 5' transcription initiation site. In this report, we describe results of analysis of the DRD4 120-bp repeat promoter polymorphism in a sample of 371 children with ADHD and their parents, using the transmission disequilibrium test (TDT). Results showed a significant preferential transmission of the 240-bp (long) allele with ADHD. Exploratory analyses of the Inattentive phenotypic subtype of ADHD strengthened the evidence for linkage. These data add further support for the role of DRD4 variants conferring increased risk for ADHD, and imply that additional studies of DRD4 and other related genes are needed.
注意缺陷多动障碍（ADHD）是一种常见的儿童期起病的神经发育障碍。双胞胎、收养及家族研究的证据支持了ADHD病因中的遗传因素。多项候选基因研究已确定多巴胺4受体基因（DRD4）外显子3中的7重复变异与ADHD之间存在关联。然而，尽管有阳性报告发现外显子3 VNTR与ADHD有关联，但DRD4内的其他几种多态性也已被确定，它们可能会增加患ADHD的风险。最近，已描述了DRD4基因的另一种常见多态性，涉及5'转录起始位点上游的120 bp重复元件。在本报告中，我们使用传递不平衡检验（TDT）描述了对371名ADHD儿童及其父母样本中DRD4 120 bp重复启动子多态性的分析结果。结果显示，240 bp（长）等位基因与ADHD存在显著的优先传递。对ADHD注意力不集中表型亚型的探索性分析加强了连锁证据。这些数据进一步支持了DRD4变异增加ADHD风险的作用，并表明需要对DRD4和其他相关基因进行更多研究。
