 |
|
|
|
Brookes, K-J., Xu, X., Anney, R. J. L., Franke,
B., Zhou, K., Chen, W., Banaschewski, T., Buitelaar, J., Ebstein, R.
P., Eisenberg, J., Gill, M., Miranda, A., Oades, R. D.,
Roeyers, H., Rothenberger, A., Sergeant, J. A., Sonuga-Barke, E. J.
S., Steinhausen, H-C., Taylor, E. A., Faraone, S. V. & Asherson,
P. Introduction: Many studies have reported an association between ADHD & the 10-repeat allele of a VNTR polymorphism in the 3'-untranslated region (UTR) of the dopamine (DA) transporter gene (DAT1). --- Yet, recent meta-analyses of available data find little or no evidence for this association although there is strong evidence for heterogeneity between data-sets. --- Such findings could arise for several-reasons including the presence of relatively rare risk alleles on common haplotype backgrounds or the functional interaction of two or more loci within the gene. --- We previously described the importance of a specific haplotype at the 3'-end of DAT1, as well as the identification of associated SNPs within or close to 5'-regulatory sequences. Methods: In the IMAGE sample -- 1,147 individuals with DSM-IV combined subtype ADHD from 988 affected probands and 150 of their affected siblings. (The initial scan of samples identified two clusters of associated SNP markers at the 3’ and 5’ ends of the gene [13]. From these we selected two SNPs from the 3’ region (rs40184 and rs3776513) and two located in the 5’ region (rs2550946 and rs11564750). Results: 2 - These findings indicate the presence of at least 2 loci associated with ADHD within the DAT1 gene & suggest that either additive or interaction effects of these 2 loci on the risk for ADHD. Discussion: Overall these data provide further evidence that genetic variants of the DA transporter gene confer an increased risk for ADHD. The data do not strongly indicate an interaction between the 5' & 3' ends of the gene, but rather the presence of 2 independent loci within the gene, (which may or may not interact). Support NIH |
