Unidad de Genética. Grupo GENIUROS. Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 N° 63C-69, Bogotá, Colombia.
Neurol Sci. 2013 Dec;34(12):2219-22. doi: 10.1007/s10072-013-1569-4. Epub 2013 Nov 1.
Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral pathology characterized by distinct degrees of inattention, hyperactivity and impulsivity. Although ADHD etiology remains elusive, the ADRA2A candidate gene underlies a particular interest, since it participates in the prefrontal cortex regulation of executive function. Three SNPs located on 5' and 3'UTR regions of the gene have been extensively explored but none of them have been definitely validated as a predisposition or a causative sequence variation. In this study, in order to determine whether ADRA2A non-synonymous sequence variants, resulting in biochemical modifications of the protein, are a common cause of the disease we sequenced the complete ADRA2A coding region in a panel of ADHD children of Colombian origin. We identified the c.1138 C>A (p.Arg380Arg) silent substitution. We conclude that ADRA2A non-synonymous sequence variants do not cause ADHD in our sample population. We cannot formerly discard a potential role of this gene during ADHD pathogenesis since only the coding region was analysed. We hope that these results will encourage further researchers to sequence the promoter and coding regions of ADRA2A in large panels of ADHD patients from distinct ethnical origins.
注意缺陷多动障碍(ADHD)是一种常见的神经行为病理学,其特征是注意力不集中、多动和冲动程度不同。尽管 ADHD 的病因仍然难以捉摸,但 ADRA2A 候选基因引起了特别关注,因为它参与了前额叶皮层对执行功能的调节。该基因的 5'和 3'UTR 区域的三个 SNP 已被广泛研究,但没有一个被明确验证为易感性或致病序列变异。在这项研究中,为了确定 ADRA2A 非同义序列变异是否导致蛋白质的生化修饰,从而成为疾病的常见原因,我们对一组哥伦比亚裔 ADHD 儿童的 ADRA2A 编码区进行了测序。我们确定了 c.1138 C>A (p.Arg380Arg) 无义取代。我们的结论是,ADRA2A 非同义序列变异不会导致我们样本人群中的 ADHD。我们不能正式排除该基因在 ADHD 发病机制中的潜在作用,因为仅分析了编码区。我们希望这些结果将鼓励更多的研究人员对来自不同种族起源的大型 ADHD 患者群体的 ADRA2A 启动子和编码区进行测序。