title: No support for association between the dopamine transporter (DAT1) gene and ADHD.
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.
authors.affiliation: Department of Psychological Medicine, School of Medicine, Cardiff University,Cardiff, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Langley
authors.forename: D
authors.initials: D
authors.lastname: Turic
authors.forename: T R
authors.initials: TR
authors.lastname: Peirce
authors.forename: S
authors.initials: S
authors.lastname: Mills
authors.forename: M B
authors.initials: MB
authors.lastname: Van Den Bree
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: M C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: A
authors.initials: A
authors.lastname: Thapar
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate