Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Pharmacogenomics J. 2013 Oct;13(5):476-80. doi: 10.1038/tpj.2012.25. Epub 2012 Jun 12.
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.
羧基酯酶 1 是参与哌醋甲酯(MPH)代谢的酶。本研究旨在评估-75T>G 多态性与注意缺陷多动障碍(ADHD)儿童食欲减退之间的关联。对 213 名患有 ADHD 的儿童进行了调查。主要结果是通过基线、治疗 1 个月和 3 个月时应用 Barkley 兴奋剂副作用评定量表测量的食欲减退。增加 MPH 剂量,直到不再出现临床改善或出现明显不良反应。G 等位基因与食欲减退评分呈关联趋势(P=0.05)。还观察到 G 等位基因与治疗时间之间对食欲减退评分的显著交互作用(P=0.03)。与 T 等位基因纯合子相比,G 等位基因携带者食欲减退恶化的风险更高(比值比=3.47,P=0.01)。本研究结果提示羧基酯酶 1-75T>G 多态性可能影响 MPH 治疗青少年 ADHD 时食欲减退的恶化。