Holmes J, Payton A, Barrett J H, Hever T, Fitzpatrick H, Trumper A L, Harrington R, McGuffin P, Owen M, Ollier W, Worthington J, Thapar A
University Department of Child and Adolescent Psychiatry, Royal Manchester Children's Hospital, UK.
Mol Psychiatry. 2000 Sep;5(5):523-30. doi: 10.1038/sj.mp.4000751.
Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition of early childhood onset characterised by marked inattention, hyperactivity and impulsiveness. Molecular genetic investigations of ADHD have found positive associations with the 480-bp allele of a VNTR situated in the 3' untranslated region of DAT1 and allele 7 of a VNTR in exon 3 of DRD4. A number of independent studies have attempted to replicate these findings but the results have been inconsistent. We used both family-based and case control approaches to examine these polymorphisms in a sample of 137 children diagnosed with ICD-10, DSM-IV or DSM-III-R ADHD. We found no evidence of association with the DAT1 polymorphism, despite a sample size that has up to 80% power to detect a previously reported effect size. We observed a significant increase in the DRD4 7 repeat allele amongst ADHD probands (21.7%) and their parents (18.9% in mothers, 22.3% in fathers), compared to ethnically matched controls (12.8%). However TDT analysis showed no preferential transmission of allele 7 to ADHD probands.
注意缺陷多动障碍（ADHD）是一种高度可遗传的儿童早期起病的精神疾病，其特征为明显的注意力不集中、多动和冲动。对ADHD的分子遗传学研究发现，位于多巴胺转运体1（DAT1）基因3'非翻译区的可变数目串联重复序列（VNTR）的480 bp等位基因以及多巴胺受体D4（DRD4）基因第3外显子中的VNTR的7等位基因与之呈正相关。许多独立研究试图重复这些发现，但结果并不一致。我们采用基于家系和病例对照的方法，对137名被诊断为符合ICD - 10、DSM - IV或DSM - III - R标准的ADHD儿童样本中的这些多态性进行了检测。尽管我们的样本量有高达80%的检验效能来检测先前报道的效应量，但我们并未发现与DAT1基因多态性存在关联的证据。与种族匹配的对照组（12.8%）相比，我们观察到ADHD先证者（21.7%）及其父母（母亲为18.9%，父亲为22.3%）中DRD4基因7重复等位基因显著增加。然而，传递不平衡检验（TDT）分析显示，7等位基因并未优先传递给ADHD先证者。
