Response to methylphenidate in adults with ADHD is associated with a polymorphism in SLC6A3 (DAT1).
In this pharmacogenetic study in adults with ADHD (n = 42), a stratified analysis was performed of the association between response to methylphenidate (MPH), assessed under double-blind conditions, and polymorphisms in the genes encoding the dopamine transporter, SLC6A3 (DAT1), the norepinephrine transporter, SLC6A2 (NET), and the dopamine receptor D4, DRD4. The VNTR polymorphism in the 3' untranslated region of SLC6A3 was significantly associated with an increased likelihood of a response to MPH treatment (OR 3.8; 95% CI 1.0-15.2, and OR 5.4; 95% CI 1.4-21.9, depending on the definition of response) in carriers of a single 10-repeat allele compared to patients with the 10/10 genotype. The polymorphisms in DRD4 and the SLC6A2 were not associated with treatment response. This study supports a role of the SLC6A3 genotype in determining the response to MPH in the treatment of adults with ADHD.
Kooij
J Sandra
JS
PsyQ, Psycho-Medical Programs, The Hague, The Netherlands. s.kooij@psyq.nl
Boonstra
A Marije
AM
Vermeulen
Sita H
SH
Heister
Angelien G
AG
Burger
Huibert
H
Buitelaar
Jan K
JK
Franke
Barbara
B
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D018592:Cross-Over Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004311:Double-Blind Method; D005838:Genotype; D006801:Humans; D008774:Methylphenidate / Q000627:therapeutic use*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics
D000697:Central Nervous System Stimulants; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D008774:Methylphenidate