Association study of promoter polymorphisms at the dopamine transporter gene in Attention Deficit Hyperactivity Disorder.
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/SLC6A3) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD.


METHODS
To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT).


RESULTS
A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (P = 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (P = 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations.


CONCLUSIONS
The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.
Xu
Xiaohui
X
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK. x.xu@iop.kcl.ac.uk
Mill
Jonathan
J
Sun
Bo
B
Chen
Chih-Ken
CK
Huang
Yu-Shu
YS
Wu
Yu-Yu
YY
Asherson
Philip
P
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors
D050483:Dopamine Plasma Membrane Transport Proteins