Pharmacogenetic Testing for Predicting Methylphenidate Treatment Outcomes in Childhood Attention Deficit Hyperactivity Disorder in Turkey: Focus on Carboxylesterase 1, Latrophilin-3, and Catechol-O-Methyltransferase

Abstract

Pharmacogenetic studies involving Carboxylesterase 1 (CES1), Latrophilin-3 (LPHN3), and Catechol-O-methyltransferase (COMT) revealed individual differences regarding therapeutic response in children with attention deficit hyperactivity disorder (ADHD) under methylphenidate (MPH) treatment. This study aimed to evaluate MPH's association with the adverse effect status in children and its relationship with CES1, LPHN3, and COMT in the Turkish population. The study included 102 children and adolescents with ADHD, who were categorized as responders, or the adverse effect group based on their treatment response. The Naranjo Adverse Drug Reaction Probability Scale evaluated the presence and severity of adverse effects. Saliva sample was taken from the patients and genotype distribution of CES1 rs3815583, CES1 rs2307227, LPHN3 rs6551665, LPHN3 rs1947274, LPHN3 rs6858066, LPHN3 rs2345039, and COMT rs4680 were examined. In the adverse effect group, instances of carrying the GG genotype in CES1 rs2307227, having G vs. T genotype and GG vs. GT were significantly higher. In LPHN3 rs2345039, carrying the C genotype vs. G was associated with a serious adverse effect. In COMT rs4680, individuals with the AA or GG genotype were significantly higher in the adverse effect group. Our study suggests a relationship between genetic polymorphisms and the side effect status in children receiving MPH.

Keywords: ADHD; adverse effect; methylphenidate; pharmacogenomics.