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Sequence variation in the 3′‐untranslated region of the dopamine transporter gene and attention‐deficit hyperactivity disorder (ADHD)
Author(s) -
Feng Yu,
Wigg Karen G.,
Makkar Rohit,
Ickowicz Abel,
Pathare Tejaswee,
Tannock Rosemary,
Roberts Wendy,
Malone Molly,
Kennedy James L.,
Schachar Russell,
Barr Cathy L.
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30190
Subject(s) - dopamine transporter , genetics , variable number tandem repeat , allele , attention deficit hyperactivity disorder , genotyping , untranslated region , polymorphism (computer science) , biology , gene , genotype , medicine , psychiatry , transporter , messenger rna
The dopamine transporter gene ( DAT1 ) has been reported to be associated with attention‐deficit hyperactivity disorder (ADHD) in a number of studies [Cook et al. (1995): Am J Human Genet 56(4):9993–998; Gill et al. (1997): Mol Psychiatry 2(4):311–313; Waldman et al. (1998): Am J Human Genet 63(6):1767–1776; Barr et al. (2001): Biol Psychiatry 49(4):333–339; Curran et al. (2001): Mol Psychiatry 6(4):425–428; Chen et al. (2003): Mol Psychiatry 8(4):393–396]. Specifically, the 10‐repeat allele of the 40‐bp variable number of tandem repeats (VNTR) polymorphism located in the 3′ untranslated region (UTR) of the gene has been found to be associated with ADHD. There is evidence from in vitro studies indicating that variability in the repeat number, and sequence variation in the 3′‐UTR of the DAT1 gene may influence the level of the dopamine transporter protein [Fuke et al. (2001): Pharmacogenomics J 1(2):152–156; Miller and Madras (2002): Mol Psychiatry 7(1):44–55]. In this study, we investigated whether DNA variation in the DAT1 3′UTR contributed to ADHD by genotyping DNA variants around the VNTR region in a sample of 178 ADHD families. These included a Msp I polymorphism (rs27072), a Dra I DNA change (T/C) reported to influence DAT1 expression levels, and a Bst UI polymorphism (rs3863145) in addition to the VNTR. We also screened the VNTR region by direct resequencing to determine if there was sequence variation within the repeat units that could account for the association. Our results indicate that DAT1 is associated with ADHD in our sample but not with alleles of the VNTR polymorphism. We did not find any variation in the sequence for either the 10‐ or 9‐repeat alleles in the probands screened nor did we observe the reported Dra I (T/C) variation. Our results therefore refute the possibility of the reported Dra I variation or alleles of the VNTR as the functional variants contributing to the disorder. © 2005 Wiley‐Liss, Inc.