Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, Aleja Powstancόw Wielkopolskich 72 St., 70-111 Szczecin, Poland.
Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Aleja Powstancόw Wielkopolskich 72 St., 70-111 Szczecin, Poland.
Int J Environ Res Public Health. 2022 Apr 8;19(8):4479. doi: 10.3390/ijerph19084479.
Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase () and dopamine receptor D2 () gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of (rs4680) and (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of (rs4680) ( = 0.04994) in all ADHD children. No effect of (rs4680) and (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed and gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.
胎儿酒精谱系障碍（FASD）是高产前酒精暴露（hPAE）的最常见发育障碍原因之一。FASD 儿童药物治疗的主要原因是注意力缺陷多动障碍（ADHD），而哌甲酯（MPH）是首选药物。本研究旨在评估是否患有 ADHD 的 hPAE 儿童，无论是否存在形态学 FASD，其儿茶酚-O-甲基转移酶（COMT）和多巴胺受体 D2（DRD2）基因多态性存在差异，以及遗传易感性是否会影响 MPH 治疗的反应和安全性。对 COMT（rs4680）和 DRD2（rs1076560、rs1800497）的多态性进行了 DNA 样本分析。在所有 ADHD 儿童中，MPH 副作用与 COMT （rs4680）的 G 等位基因之间存在相关性，具有边缘统计学意义（=0.04994）。未观察到 COMT （rs4680）和 DRD2 （rs1076560、rs1800497）多态性和治疗效果的影响。分析的 COMT 和 DRD2 基因多态性似乎在 hPAE 儿童 ADHD 中对 MPH 疗效没有作用，而低活性（Met158）变体携带者可能对 MPH 的耐受性较差。MPH 治疗在 ADHD 中是有效的，而与 FASD 无关，尽管 ADHD-FASD 变体需要更高的剂量才能成功。这些结果可能有助于儿童精神病学的优化和个体化。
