Genro Júlia P, Zeni Cristian, Polanczyk Guilherme V, Roman Tatiana, Rohde Luis A, Hutz Mara H
Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):215-9. doi: 10.1002/ajmg.b.30428.
The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission and is also the major site of action for methylphenidate which is one of the main drugs used to treat attention deficit hyperactivity disorder (ADHD). Most association studies with ADHD have concentrated on the 3'-untranslated region of the gene (3'-UTR) mainly in a variable number of tandem repeat (VNTR) polymorphism, but these investigations have reported discordant results. In this study, we tested this VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using family-based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D' = 0.56; P = 0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P = 0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P = 0.004). Our results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample.
多巴胺转运体（DAT）在多巴胺能神经传递的调节中起关键作用，也是哌甲酯的主要作用位点，哌甲酯是用于治疗注意力缺陷多动障碍（ADHD）的主要药物之一。大多数针对ADHD的关联研究主要集中在该基因的3'-非翻译区（3'-UTR），主要是可变数目的串联重复序列（VNTR）多态性，但这些研究报告的结果并不一致。在本研究中，我们在243名巴西ADHD儿童和青少年及其父母的样本中，使用基于家系的关联分析测试了这种VNTR多态性以及另一种启动子多态性-839 C>T（Rs：2652511）。在该样本中未检测到这两种多态性之间存在显著的连锁不平衡（D' = 0.56；P = 0.22）。未发现与VNTR多态性相关的证据。在总样本中观察到-839 C>T多态性的C等位基因向ADHD儿童的偏向传递存在显著关联（P = 0.03），当分析仅限于ADHD混合型时，这种关联得到加强（P = 0.004）。我们的结果表明，在这个巴西样本中，DAT1基因的启动子区域在ADHD易感性中起作用。
