Association of the dopamine transporter gene (DAT1) with poor methylphenidate response.
OBJECTIVE
This study attempted to relate the alleles of the D2 (DRD2), D4 (DRD4), and dopamine transporter (DAT1) genes to the behavioral outcome of methylphenidate therapy.


METHODS
African-American children with attention-deficit hyperactivity disorder were treated with methylphenidate in doses not in excess of 60 mg/day. The dosage was increased until behavioral change was achieved, using a decrement in scores of less than or equal to 1 on a commonly used rating scale or until the maximum tolerated dose was achieved. Blood samples were obtained at that point, and genotypes for polymorphism at the respective genes were identified.


RESULTS
Genotypes were then tested by chi 2 to assess the significance of any association with drug response. Only the dopamine transporter gene was found to be significant. Homozygosity of the 10-repeat allele was found to characterize nonresponse to methylphenidate therapy (p = .008).


CONCLUSIONS
While the results suggest that alleles of the dopamine transporter gene play a role in methylphenidate response, replication in additional studies is needed.
Winsberg
B G
BG
Division of Child Psychiatry and Pediatrics, Brookdale University Hospital and Medical Center, Brooklyn, NY 11212, USA.
Comings
D E
DE
D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D015259:Dopamine Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D001741:Black or African American
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate