期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 144B, 期 8, 页码 1070-1078出版社
WILEY
DOI: 10.1002/ajmg.b.30572
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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.
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