Pharmacogenetics of methylphenidate response in attention deficit/hyperactivity disorder: association with the dopamine transporter gene (SLC6A3).
Pharmacogenetic studies investigating the 40-bp VNTR polymorphism at SLC6A3 and methylphenidate response have shown conflicting results and large differences in study design and efficacy endpoints. Our objective was to investigate the relation between the 3'-VNTR at SLC6A3 and variability in methylphenidate response in a sample of 141 ADHD children and adolescents, assessed before and after methylphenidate treatment with both clinical and neuropsychological outcome measures. 10-R homozygotes were significantly overrepresented in the low response group, but no genotype effect was shown in cognitive variables improvement. A meta-analysis of pharmacogenetic studies with comparable data (responders vs. non-responders) on a total of 475 subjects showed a significant association between the 10-10 genotype and low rates of methylphenidate response (mean Odds Ratio = 0.46; 95% CI [0.28-0.76]). Heterogeneity between these studies did not reach a significant level but, as publications with different endpoints were excluded from this meta-analysis, our results do not rule out a possible influence of study design.
AP-HP, Robert Debré Hospital, Paris, France. diane.ouakil-purper@orange.fr
D
D
Purper-Ouakil
M
M
Wohl
S
S
Orejarena
S
S
Cortese
C
C
Boni
M
M
Asch
M C
MC
Mouren
P
P
Gorwood
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D002648:Child; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D015201:Meta-Analysis as Topic; D008774:Methylphenidate / Q000627:therapeutic use*; D018895:Microsatellite Repeats; D016017:Odds Ratio; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D011336:Probability; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate; D004247:DNA