Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD

Z. Nemoda, Nora Angyal, Zsanett Tarnok, J. Gádoros, M. Sasvári

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)731-733
Number of pages3
JournalNeuropharmacology
Volume57
Issue number7-8
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Carboxylesterase
Methylphenidate
Attention Deficit Disorder with Hyperactivity
Genes
Enzymes
Genotype
Cytochrome P-450 CYP2D6
Impulsive Behavior
Pharmacogenetics
Heterozygote
Catecholamines
Meta-Analysis
Alleles
Therapeutics
Pharmaceutical Preparations
Population

Keywords

  • Attention deficit hyperactivity disorder (ADHD)
  • Carboxylesterase 1 (CES1)
  • Methylphenidate (MPH)
  • Pharmacogenetics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD. / Nemoda, Z.; Angyal, Nora; Tarnok, Zsanett; Gádoros, J.; Sasvári, M.

In: Neuropharmacology, Vol. 57, No. 7-8, 12.2009, p. 731-733.

Research output: Contribution to journalArticle

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