Feng Y, Crosbie J, Wigg K, Pathare T, Ickowicz A, Schachar R, Tannock R, Roberts W, Malone M, Swanson J, Kennedy J L, Barr C L
Department of Psychiatry, Cellular and Molecular Division, The Toronto Western Research Institute, University Health Network, Toronto, ON, Canada.
Mol Psychiatry. 2005 Nov;10(11):998-1005, 973. doi: 10.1038/sj.mp.4001722.
The synaptosomal-associated protein of 25 kDa gene (SNAP25) has been suggested as a genetic susceptibility factor in attention-deficit hyperactivity disorder (ADHD) based on the mouse strain coloboma. This strain is hemizygous for the SNAP25 gene and displays hyperactivity that responds to dextroamphetamine, but not to methylphenidate. Previously, we reported association of SNAP25 and ADHD using two polymorphisms. To further investigate this gene, we screened the exons for DNA variation and genotyped ten additional polymorphisms in an expanded sample of families from Toronto and a second sample of families collected in Irvine, CA. Significant results were observed in the Toronto sample for four markers, although not in the Irvine sample. The paper discusses the possible influence of the selection criteria on these differential results. The Irvine sample selected subjects that met the DSM-IV combined subtype diagnosis, whereas the Toronto sample included all subtypes. Analysis of the DSM-IV subtypes in the Toronto sample indicated that the differential results were not attributable to ADHD subtype. Differences in ethnicity, differential medication response, and other clinical characteristics of the samples cannot be ruled out at this time. Quantitative analysis of the dimensions of hyperactivity/impulsivity and inattention in the Toronto sample found that both behavioral traits were associated with SNAP25. Our findings continue to support SNAP25 in the susceptibility to ADHD.
基于小鼠品系无眼畸形，25kDa基因的突触体相关蛋白（SNAP25）被认为是注意力缺陷多动障碍（ADHD）的一个遗传易感性因素。该品系对于SNAP25基因是半合子，表现出对右旋苯丙胺有反应的多动，但对哌甲酯无反应。此前，我们利用两个多态性报道了SNAP25与ADHD的关联。为了进一步研究该基因，我们在来自多伦多的一个扩大的家系样本以及在加利福尼亚州欧文市收集的第二个家系样本中，对外显子进行了DNA变异筛查，并对另外十个多态性进行了基因分型。在多伦多样本中观察到四个标记有显著结果，尽管在欧文样本中未观察到。本文讨论了选择标准对这些差异结果可能产生的影响。欧文样本选择的是符合《精神疾病诊断与统计手册》第四版（DSM-IV）混合型诊断的受试者，而多伦多样本包括了所有亚型。对多伦多样本中DSM-IV亚型的分析表明，差异结果并非归因于ADHD亚型。目前不能排除样本在种族、药物反应差异以及其他临床特征方面的差异。对多伦多样本中多动/冲动和注意力不集中维度的定量分析发现，这两种行为特征均与SNAP25相关。我们的研究结果继续支持SNAP25与ADHD易感性有关。
