Get access

Relationship between VNTR polymorphisms of the human dopamine transporter gene and expression in post-mortem midbrain tissue

Authors

  • Keeley J. Brookes,

    1. MRC Social Genetic Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, United Kingdom
    Search for more papers by this author
  • Benjamin M. Neale,

    1. MRC Social Genetic Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, United Kingdom
    Search for more papers by this author
  • Karen Sugden,

    1. MRC Social Genetic Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, United Kingdom
    Search for more papers by this author
  • Nadeem Khan,

    1. Brain Bank, Department of Neuropathology, Institute of Psychiatry, King's College London, United Kingdom
    Search for more papers by this author
  • Philip Asherson,

    1. MRC Social Genetic Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, United Kingdom
    Search for more papers by this author
  • Ursula M. D'Souza

    Corresponding author
    1. MRC Social Genetic Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, King's College London, United Kingdom
    • MRC Social Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, United Kingdom.
    Search for more papers by this author

  • Please cite this article as follows: Brookes KJ, Neale BM, Sugden K, Khan N, Asherson P, D'Souza UM. 2007. Relationship Between VNTR Polymorphisms of the Human Dopamine Transporter Gene and Expression in Post-Mortem Midbrain Tissue. Am J Med Genet Part B 144B:1070–1078.

  • The authors declare that they have no competing interests.

Abstract

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. © 2007 Wiley-Liss, Inc.

Ancillary