Relationship between VNTR Polymorphisms of the human dopamine transporter gene and expression in post-mortem midbrain tissue
Relationship between VNTR Polymorphisms of the human dopamine transporter gene and expression in post-mortem midbrain tissue
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DOI：
10.1002/ajmg.b.30572
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发表时间：
2007-12-05
影响因子：
2.8
通讯作者：
D'Souza, Ursula M.
中科院分区：
文献类型：
--
作者：
Brookes, Keeley J.;Neale, Benjamin M.;D'Souza, Ursula M.
注意缺陷多动障碍（ADHD）是目前最常见的儿童行为障碍之一。这种疾病被发现是高度遗传的，表明有很大的遗传成分。相关研究已经反复暗示多巴胺转运蛋白（DAT 1）基因，特别是可变数目串联重复序列（VNTR）多态性的10-重复等位基因。位于基因的3 'UTR。从几个早期的研究中已经产生了不确定的数据，这种多态性的功能影响。因此，需要进一步研究，因此关注TaqMan RT-PCR检测的数据。测量来自死后中脑组织的DAT 1基因的表达水平与存在于3 'UTR VNTR处的多态性以及位于该基因内含子8内的另一VNTR标记（Int 8 VNTR）的关系。研究结果表明，3 'UTR VNTR的10-重复等位基因，内含子8 VNTR的3-重复和两个VNTR标记的存在与死亡后中脑中DAT 1转录物水平的增加相关。组织.使用线性回归（LR）的进一步工作表明与相关性分析一致，并且在该方向上具有名义显著性或趋势。考虑到样本量较小，计算LR的Bootstrapping-derived置信区间。这些经验分析表明，3 'UTR VNTR对相对DAT 1表达显示出显著的主效应。此外，发现组合模型（3 'UTR和Int 8 VNTR标记物）对表达的显著影响。这些数据提供了进一步的证据，合理的分子机制的病因的障碍。(c)2007 Wiley-Liss，Inc.
Attention deficit hyperactivity disorder (ADHD) is currently one of the most prevalent childhood behavioral disorders. The disorder is found to be highly heritable, suggesting a large genetic component. Association studies have repeatedly implicated the dopamine transporter (DAT1) gene, and in particular the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism. located in the 3'UTR of the gene. Inconclusive data has been generated from several earlier studies on the functional effects of this polymorphism. Therefore, there is call for further investigation and thus the focus on data described here from TaqMan RT-PCR assays. The expression levels of the DAT1 gene from post-mortem midbrain tissue was measured in relation to the polymorphism present at the 3'UTR VNTR, together with a further VNTR marker located within intron 8 of the gene (Int8 VNTR). The findings suggest that the presence of the 10-repeat allele of the 3'UTR VNTR, the 3-repeat of the intron 8 VNTR and both VNTR markers are correlated with increased levels of the DAT1 transcript in midbrain post-mortem. tissue. Further work using linear regression (LR) shows agreement with the correlation analysis, and either nominal significance or a trend in that direction. Given the small sample size, bootstrapping-derived confidence intervals were calculated for the LR. These empirical analyses suggest that the 3'UTR VNTR to show a significant main effect on relative DAT1 expression. Furthermore, a significant effect was found for the combined model (3'UTR and Int8 VNTR markers) on expression. These data provide further evidence on the plausible molecular mechanism underlying the aetiology of the disorder. (c) 2007 Wiley-Liss, Inc.