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Neuropharmacology. 2009 Dec;57(7-8):731-3. doi: 10.1016/j.neuropharm.2009.08.014. Epub 2009 Sep 4.

Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD.

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  • 1Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary. zsofia.nemoda@eok.sote.hu


Methylphenidate (MPH) is the most frequently prescribed drug in the treatment of attention deficit hyperactivity disorder (ADHD). Several pharmacogenetic studies suggested that catecholamine candidate genes influence individual MPH-responses, but these results are mostly contradictory. Genetic analyses of MPH metabolizing carboxylesterase 1 enzyme (CES1) have not been carried out, whereas, meta-analysis of CYP2D6 genetic variants has been already indicated significant pharmacogenetic differences in atomoxetine treatment. Here we present an association analysis of the CES1 Gly143Glu functional polymorphism in a Hungarian ADHD group (n = 173). The genotype frequencies were similar to that of the general population (5.8% vs 4.1% of Gly/Glu heterozygote). Pharmacogenetic analysis was conducted among 122 ADHD children treated with MPH. Neither the categorical analysis comparing 90 responders vs 32 non-responders, nor the dimensional analysis of Inattention and Hyperactivity-Impulsivity score reduction showed a significant main genotype effect. However, analyzing the daily dose, we observed an association with the rare 143Glu-variant: 5 patients in the responder group carrying the Glu-allele required lower doses of MPH for symptom reduction (0.410 +/- 0.127 vs 0.572 +/- 0.153 mg/kg, t(1,88) = 2.33, p = 0.022). This result warrants for further investigations of the CES1 gene in larger ADHD samples.

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