Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD
Zsofia Nemoda1, Nora Angyal, Zsanett Tarnok
1Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary. zsofia.nemoda@eok.sote.hu
Neuropharmacology
|September 8, 2009
Summary
The CES1 Gly143Glu polymorphism may influence methylphenidate (MPH) dosage in children with attention deficit hyperactivity disorder (ADHD). Carriers of the rare 143Glu variant required lower MPH doses for symptom reduction.
Area of Science:
- Pharmacogenetics
- Neuroscience
- Genetics
Background:
- Methylphenidate (MPH) is a primary treatment for attention deficit hyperactivity disorder (ADHD).
- Previous pharmacogenetic studies on MPH response have yielded contradictory results.
- Genetic associations with MPH metabolism, specifically CES1, remain largely unexplored.
Purpose of the Study:
- To investigate the association of the CES1 Gly143Glu functional polymorphism with MPH response in Hungarian ADHD patients.
- To explore the role of CES1 in individual differences in MPH treatment outcomes.
Main Methods:
- Association analysis of the CES1 Gly143Glu polymorphism in 173 Hungarian ADHD patients.
- Pharmacogenetic analysis in 122 ADHD children treated with MPH, assessing responders vs. non-responders and symptom reduction.
- Analysis of daily MPH dose in relation to genotype.
Main Results:
- Genotype frequencies of CES1 Gly143Glu were similar to the general population.
- No significant main genotype effect was found for categorical or dimensional MPH response.
- However, ADHD patients with the rare 143Glu variant in the responder group required significantly lower MPH doses (0.410 mg/kg) compared to Gly/Gly homozygotes (0.572 mg/kg).
Conclusions:
- The CES1 Gly143Glu polymorphism may influence MPH dosage requirements in ADHD treatment.
- The rare 143Glu allele is associated with reduced MPH dosage for effective symptom control.
- Further investigation in larger ADHD cohorts is warranted to confirm these findings.
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