Association of the 480 bp DAT1 allele with methylphenidate response in a sample of Irish children with ADHD.
Several studies have implicated the dopamine transporter gene (DAT1) as conferring susceptibility to attention deficit hyperactivity disorder (ADHD), in particular, a VNTR situated at the 3' end of the gene. In addition, the 10-repeat VNTR allele associated with ADHD has been reported to be associated with an over-active transporter protein (DAT). Thus children possessing this variant might be particularly responsive to methylphenidate, a drug known to act by blocking DAT. We have examined this hypothesis and now report an association between the 10-repeat VNTR DAT1 polymorphism and retrospectively rated methylphenidate response in a sample of 119 Irish children with ADHD (chi(2) = 7.918, df = 1, P = 0.005). Our findings suggest a role for the 10-repeat DAT1 risk allele in medication response and may help to predict positive clinical outcome in ADHD.
Kirley
Aiveen
A
Departments of Psychiatry and Genetics, Trinity College Dublin, Dublin, Ireland. akirley@tcd.ie
Lowe
Naomi
N
Hawi
Ziarih
Z
Mullins
Celine
C
Daly
Grainne
G
Waldman
Irwin
I
McCarron
Mary
M
O'Donnell
Deirdre
D
Fitzgerald
Michael
M
Gill
Michael
M
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; D005260:Female; D006801:Humans; D007494:Ireland; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics*; D008774:Methylphenidate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate