Pharmacogenetics of methylphenidate response in attention deficit/hyperactivity disorder: Association with the dopamine transporter gene (SLC6A3)

Purper-Ouakil, D., Wohl, M., Orejarena, S., Cortese, S., Boni, C., Asch, M., Mouren, M.C. and Gorwood, P. (2008) Pharmacogenetics of methylphenidate response in attention deficit/hyperactivity disorder: Association with the dopamine transporter gene (SLC6A3). [in special issue: Genetics of ADHD Dedicated to the Memory of Richard Todd] American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 147B (8), 1425-1430. (doi:10.1002/ajmg.b.30809). (PMID:18563707)

Abstract

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

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Contributors

Author: S. Cortese

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