Abstract
Carboxylesterase 1 is the enzyme involved in methylphenidate (MPH) metabolism. The aim of this study was to evaluate the association between a −75 T>G polymorphism and appetite reduction in children with attention-deficit/hyperactivity disorder (ADHD). A sample of 213 children with ADHD was investigated. The primary outcome was appetite reduction measured by the Barkley Stimulant Side Effect Rating Scale applied at baseline, at 1 and 3 months of treatment. MPH doses were augmented until no further clinical improvement or significant adverse events occurred. The G allele presented a trend for association with appetite reduction scores (P=0.05). A significant interaction between the G allele and treatment over time for appetite reduction scores was also observed (P=0.03). The G allele carriers presented a higher risk for appetite reduction worsening when compared with T allele homozygotes (odds ratio=3.47, P=0.01). The present results suggest an influence of carboxylesterase 1 −75 T>G polymorphism on the worsening of appetite reduction with MPH treatment in youths with ADHD.
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Acknowledgements
We thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Coordenação de Pessoal de Nível Superior (CAPES, Brazil), Fundação de Amparo a Pesquisa de São Paulo (FAPESP) and Financiadora de Estudos e Projetos (FINEP, Brazil) for financial support.
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Dr Rohde was on the speakers’ bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis and Shire in the last 3 years (less than U$ 10 000 per year and reflecting less than 5% of his gross income per year). He also received travel awards (air tickets and hotel) for taking part of two child psychiatric meetings from Novartis and Janssen-Cilag in 2010. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Abbott, Bristol-Myers Squibb, Eli-Lilly, Janssen-Cilag, Novartis and Shire. All other authors report no biomedical financial interest or potential conflict of interest.
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Bruxel, E., Salatino-Oliveira, A., Genro, J. et al. Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate. Pharmacogenomics J 13, 476–480 (2013). https://doi.org/10.1038/tpj.2012.25
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DOI: https://doi.org/10.1038/tpj.2012.25
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