No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder.
OBJECTIVE
Three studies to date have found evidence (or a trend for evidence) of linkage and association between the long allele of the 44 base pair repeat insertion/deletion 5-HTT functional polymorphism (5-HTTLPR) and attention deficit hyperactivity disorder (ADHD). In an attempt to replicate these findings, we examined this polymorphism and a variable number tandem repeat in the second intron of 5-HTT for association with ADHD.


METHODS
One hundred and fifty children who met diagnostic criteria for ADHD and their parents (where available) were genotyped for these polymorphisms. Analysis was undertaken using the transmission disequilibrium test and haplotype analysis, as well as case-control comparisons using a control group of 121 individuals.


RESULTS
No association between either the 5-HTTLPR or the variable number tandem repeat (VNTR) in ADHD was found (extended transmission disequilibrium test; P=0.37 and P=0.62, respectively). Haplotype analysis was also non-significant. Further analysis revealed no evidence of association in the subgroups of those without conduct disorder and in medication non-responders.


CONCLUSIONS
Failure to replicate findings from previous studies may be due to a lack of statistical power. However, given recent findings by Kent et al. (2002) of association with another polymorphism in the 5HTT gene, we hypothesise that previous positive findings may have arisen by the LPR and VNTR being in linkage disequilibrium with the true susceptibility polymorphism.
Langley
Kate
K
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK. thapar@cf.ac.uk
Payton
Antony
A
Hamshere
Marian L
ML
Pay
Helen M
HM
Lawson
Deborah C
DC
Turic
Darko
D
Ollier
William
W
Worthington
Jane
J
Owen
Michael J
MJ
O'Donovan
Michael C
MC
Thapar
Anita
A
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats; D009419:Nerve Tissue Proteins; D010290:Parents; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA