Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate

• Published in: The pharmacogenomics journal Vol. 13; no. 5; pp. 476 - 480
• Main Authors: Bruxel, E M, Salatino-Oliveira, A, Genro, J P, Zeni, C P, Polanczyk, G V, Chazan, R, Rohde, L A, Hutz, M H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2013; Nature Publishing Group
• Subjects: 692/699/476/1311; 692/700/1720; 692/700/565/1436/434; Adolescent; Alleles; Appetite - drug effects; Appetite - genetics; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Biomedical and Life Sciences; Biomedicine; Carboxylesterase; Carboxylic Ester Hydrolases - genetics; Care and treatment; Child; Children; Complications and side effects; Esterases; Female; Gene Expression; Genetic aspects; Genetic polymorphisms; Health aspects; Homozygote; Homozygotes; Human Genetics; Humans; Hyperactivity; Identification and classification; Male; Methylphenidate; Methylphenidate - adverse effects; Methylphenidate - therapeutic use; Methylphenidate hydrochloride; Oncology; original-article; Pharmacotherapy; Polymorphism; Polymorphism, Genetic; Psychopharmacology; methylphenidate; appetite reduction; attention deficit hyperactivity disorder; adverse reaction; carboxylesterase 1; pharmacogenetics
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/tpj.2012.25

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.