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

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...

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Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2005-11, Vol.139B (1), p.7-10
Main Authors: Langley, K., Turic, D., Peirce, T.R., Mills, S., Van Den Bree, M.B., Owen, M.J., O'Donovan, M.C., Thapar, A.
Format: Article
Language:English
Subjects:
Adolescent
Attention Deficit Disorder with Hyperactivity - drug therapy
Attention Deficit Disorder with Hyperactivity - genetics
attention deficit hyperactivity disorder (ADHD)
Central Nervous System Stimulants - pharmacology
Child
Dopamine Plasma Membrane Transport Proteins - genetics
dopamine transporter (DAT1)
Female
haplotype
Humans
Male
medication response
Methylphenidate - pharmacology
Minisatellite Repeats
Polymorphism, Single Nucleotide
promoter polymorphism
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Summary: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 (χ2 = 0.1 (df 1), P = 0.9, (odds ratio (OR) = 1.0, 95% CI 0.8–1.2), and case‐control analysis (χ2 = 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 (χ2 = 3.93, (df 9) global P = 0.85). Finally, no association was found between the DAT 1 VNTR and response to stimulant medication (χ2 = 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. © 2005 Wiley‐Liss, Inc.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.30206