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PMID: 16082688 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

No support for association between the dopamine transporter (DAT1) gene and ADHD.

Langley K, Turic D, Peirce TR, Mills S, Van Den Bree MB, Owen MJ, O'Donovan MC, Thapar A

Abstract

Several groups have reported an association between the 10-repeat allele of a dopamine transporter (DAT1) 3'UTR VNTR variant and ADHD but the finding has not been universally observed. An association between DAT1 genotype and stimulant medication response has also been reported although again there are conflicting data. We tested the DAT1 3'VNTR and three SNPs in the putative promoter region of DAT1 for association with ADHD in 263 parent-proband trios. Analyses of genotypes, alleles, and haplotypes were performed using family-based association methods. Case-control analysis of the VNTR in 263 cases and 287 controls was also conducted. In addition, we tested for association between the VNTR marker and stimulant medication response. Comparing allele 10 versus all other alleles combined, no significant association was found with ADHD, using FBAT analysis (chi2 = 0.1 (df 1), P = 0.9, (odds ratio (OR) = 1.0, 95% CI 0.8-1.2), and case-control analysis (chi2 = 0.12 (df 2), P = 0.91). No evidence of association with any of the SNPs in the promoter region was found. Haplotype analysis was also non-significant (chi2 = 3.93, (df 9) global P = 0.85). Finally, no association was found between the DAT 1 VNTR and response to stimulant medication (chi2 = 1.63 (df 3) P = 0.65). We conclude that the 3' VNTR and three additional promoter variants in DAT1 do not appear to be associated with ADHD, or response to stimulant mediation in our sample.

MeSH Terms
Adolescent Attention Deficit Disorder with Hyperactivity/drug therapy,genetics Central Nervous System Stimulants/pharmacology Child Dopamine Plasma Membrane Transport Proteins/genetics Female Humans Male Methylphenidate/pharmacology Minisatellite Repeats Polymorphism, Single Nucleotide
Chemicals
Central Nervous System Stimulants Dopamine Plasma Membrane Transport Proteins SLC6A3 protein, human Methylphenidate
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Langley K
Department of Psychological Medicine, School of Medicine, Cardiff University,Cardiff, United Kingdom.
Turic D
Peirce T R
Mills S
Van Den Bree M B
Owen M J
O'Donovan M C
Thapar A
Article Info
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Abbr.
Am J Med Genet B Neuropsychiatr Genet
ISSN
1552-4841
Published
2005-11-05
Pages
7-10
Language
English
Region
United States
NLM ID
101235742
Subset
IM
Grants
Medical Research Council · G9810900 · United Kingdom
Wellcome Trust · United Kingdom
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