Sunohara G A, Roberts W, Malone M, Schachar R J, Tannock R, Basile V S, Wigal T, Wigal S B, Schuck S, Moriarty J, Swanson J M, Kennedy J L, Barr C L
Neurogenetics Section, The Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
J Am Acad Child Adolesc Psychiatry. 2000 Dec;39(12):1537-42. doi: 10.1097/00004583-200012000-00017.
There is considerable evidence supporting a genetic component in the etiology of attention-deficit/hyperactivity disorder (ADHD). Because stimulant medications act primarily on the dopaminergic system, dopamine system genes are prime candidates for genetic susceptibility factors for ADHD. Previous studies by several groups have observed a significant association of ADHD and an allele with 7 copies of the 48 base pair repeat in the third exon of the dopamine D4 receptor.
The authors sought to replicate these previous findings by collecting an independent sample of families from Toronto, Ontario, Canada, and confirming this finding in an expanded sample of ADHD families collected from Irvine, California. Using the transmission disequilibrium test (TDT), the authors tested for biased transmission of the 7-repeat allele at the exon III polymorphism of the dopamine D4 receptor locus in these samples of ADHD subjects.
Biased transmission of the 7-repeat allele from parents to ADHD probands and their affected siblings was observed in the 2 new samples of families collected in Toronto and Irvine (TDT chi2 = 2.711, 1 df, one-sided p value = .050) and for these samples combined with the 52 families previously reported from Irvine (TDT chi2 = 6.426, 1 df, one-sided p value = .006).
The results of this study further support the possibility of a role of the dopamine D4 receptor locus in ADHD.
有大量证据支持注意缺陷多动障碍（ADHD）病因中的遗传因素。由于兴奋剂药物主要作用于多巴胺能系统，多巴胺系统基因是ADHD遗传易感性因素的主要候选基因。几个研究小组之前的研究观察到ADHD与多巴胺D4受体第三外显子中48个碱基对重复序列有7个拷贝的等位基因之间存在显著关联。
作者试图通过收集来自加拿大安大略省多伦多市的独立家庭样本，并在从加利福尼亚州欧文市收集的扩大的ADHD家庭样本中证实这一发现，来复制这些先前的研究结果。作者使用传递不平衡检验（TDT），在这些ADHD受试者样本中检测多巴胺D4受体基因座外显子III多态性处7重复等位基因的偏态传递。
在多伦多和欧文市收集的2个新家庭样本中观察到7重复等位基因从父母向ADHD先证者及其受影响的兄弟姐妹的偏态传递（TDT卡方 = 2.711，1自由度，单侧p值 = 0.050），并且对于这些样本与之前报道的来自欧文市的52个家庭相结合的情况（TDT卡方 = 6.426，1自由度，单侧p值 = 0.006）。
本研究结果进一步支持多巴胺D4受体基因座在ADHD中起作用的可能性。
