Biotechnology and Genetic Engineering Unit, College of Medicine, Taif University, Taif, Kingdom of Saudi Arabia.
Mol Biol Rep. 2012 Dec;39(12):11081-6. doi: 10.1007/s11033-012-2012-2. Epub 2012 Oct 18.
Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders characterized by inattention, hyperactivity and impulsivity. In Saudi Arabia the prevalence of combined ADHD is 16.4 %. ADHD etiology is not clear and not completely understood. There are several evidences for involvement of dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters. Dopamine Transporter 1 (DAT1) plays an important role in controlling blood levels of dopamine. The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30 bp-promoter VNTR and DAT1 40 bp 3' UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95 % confidence interval (95 % CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P < 0.01, OR = 3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P < 0.01, OR = 2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P < 0.01, OR = 4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis. This is the first report investigated the association between MAOA and DAT1 polymorphism at molecular level in Saudi Arabia population as well as Arab world. Therefore further studies are needed to generalize obtained results at Saudi Arabia.
注意缺陷多动障碍（ADHD）是最常见的儿童行为障碍之一，其特征为注意力不集中、多动和冲动。在沙特阿拉伯，混合性 ADHD 的患病率为 16.4%。ADHD 的病因尚不清楚，也不完全了解。多巴胺能、5-羟色胺能和去甲肾上腺素能神经递质系统在 ADHD 的发病机制中都有涉及。单胺氧化酶 A（MAOA）参与了这三种神经递质的降解。多巴胺转运体 1（DAT1）在控制多巴胺的血液水平方面起着重要作用。本研究的目的是探讨 MAOA 的 30 bp-启动子 VNTR 和 DAT1 的 40 bp 3'UTR VNTR 多态性与沙特人群中 ADHD 之间的关联。采用 PCR 技术检测了 120 例 ADHD 患者和 160 例对照的 MAOA 和 DAT1 基因多态性。比较了 ADHD 患者与对照组中 MAOA 和 DAT1 多态性的等位基因和基因型频率。通过比值比（OR）检验和 95%置信区间（95%CI）来估计关联程度，检验 ADHD 与每个研究多态性的等位基因和基因型之间的关联。发现 MAOA 的两种基因型 3/4 和 3/2 与 ADHD 显著相关（P<0.01，OR=3，4.9），为风险效应。未发现 MAOA 等位基因与 ADHD 之间存在显著关联。在 DAT1 多态性中，两种等位基因（7 和 11 个重复）（P<0.01，OR=2.5 和 3.3）以及两种基因型（11/11 和 11/7）（P<0.01，OR=4，3）与 ADHD 显著相关，为风险效应。相反，9 和 10 个重复显示出显著的保护作用，10/10 和 10/9 基因型也是如此。这些发现支持了这样一种假说，即 MAOA 和 DAT1 的某些多态性在沙特人群中具有导致 ADHD 发展的因果作用。另一种多态性则没有支持这一假说。这是首次在沙特阿拉伯人群以及阿拉伯世界研究 MAOA 和 DAT1 多态性与 ADHD 之间的分子水平关联。因此，需要进一步的研究来推广在沙特阿拉伯获得的结果。
