Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder

C. L. Barr, C. Xu, J. Kroft, Y. Feng, K. Wigg, G. Zai, R. Tannock, R. Schachar, M. Malone, W. Roberts, M. M. Nöthen, F. Grünhage, D. J. Vandenbergh, G. Uhl, G. Sunohara, N. King, J. L. Kennedy

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is often treated using methylphenidate, a psychostimulant that inhibits the dopamine transporter. This led E.H. Cook and colleagues to consider the dopamine transporter locus (DAT1) as a primary candidate gene for ADHD. That group reported a significant association between ADHD and the 480-base pair (bp) allele of the variable number of tandem repeats (VNTR) polymorphism located in the 3′ untranslated region of the DAT1 gene. This association was later replicated in additional studies. Methods: The DAT1 gene has additional common polymorphisms in intron 9 and exon 9. We investigated the possibility of linkage of DAT1 and ADHD using the VNTR polymorphism and two additional common polymorphisms in 102 nuclear families with an ADHD proband. Using the transmission disequilibrium test, we examined the transmission of the alleles of each of these polymorphisms, as well as the haplotypes of the polymorphisms. Results: We did not observe significant evidence for the biased transmission of the alleles of either the VNTR or the additional two polymorphisms when examined individually, although there was a trend for the biased transmission of the 480-bp allele of the VNTR. When we examined the haplotypes of the three polymorphisms we found significant evidence for biased transmission of one of the haplotypes containing the 480-bp VNTR allele. We also genotyped six additional DNA sequence variants of the DAT1 gene. However, these variants were not sufficiently polymorphic in our sample to be informative. Two of the DNA variants that result in an amino acid change, Ala559Val and Glu602Gly, were not observed in our sample. Conclusions: Our results support previous findings of an association between the DAT1 gene and ADHD.

Original languageEnglish (US)
Pages (from-to)333-339
Number of pages7
JournalBiological Psychiatry
Volume49
Issue number4
DOIs
StatePublished - Feb 15 2001
Externally publishedYes

Keywords

  • Attention-deficit/hyperactivity disorder
  • Dopamine transporter
  • Genetics
  • Haplotypes
  • Polymorphism
  • Transmission disequilibrium test

ASJC Scopus subject areas

  • Biological Psychiatry

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