Evaluation of dopamine transporter gene variations in Turkish children with attention deficit hyperactivity disorder treated with methylphenidate adverse effects

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Aim Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder, with methylphenidate (MPH) as the first-line treatment. MPH primarily exerts its effects by inhibiting the dopamine transporter (DAT); therefore, variants in the DAT1 gene may affect susceptibility to its adverse effects.Methods This study included 47 children and adolescents diagnosed with ADHD according to DSM-5-TR criteria who were receiving MPH treatment. MPH-related adverse effects were assessed using the Barkley Stimulants Side Effects Rating Scale. Participants were categorized into groups based on whether they experienced adverse effects. The exons of the DAT1 gene were sequenced using NGS.Results A total of 16 variants were identified in the DAT1 gene, including intronic, untranslated region, synonymous, splice-region, and splice polypyrimidine tract variants. One rare intronic deletion variant, c.1032-44_1032-42del, was classified as a VUS. Genetic association analyses identified significant associations for rs1042098 under the genotypic (p = 0.003; BH q = 0.019) and dominant (p = 0.037; BH q = 0.091) models, and for rs6876890 under the genotypic model (p = 0.008; BH q = 0.044).Conclusions Our findings suggest that specific DAT1 gene polymorphisms, particularly rs1042098 and rs6876890, may be associated with MPH-related adverse effects in children and adolescents with ADHD.

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