Prader-Willi syndrome (PWS) is associated with co-morbid psychiatric symptoms (disruptive behavior, anxiety, mood disorders, and psychosis) often requiring psychotropic medications. In this clinical case series of 35 patients with PWS, pharmacogenetic testing was obtained to determine allele frequencies predicting variations in activity of cytochrome (CYP) P450 drug metabolizing enzymes 2D6, 2B6, 2C19, 2C9, 3A4, and 1A2. Results were deidentified, collated, and analyzed by PWS genetic subtype: 14 deletion (DEL), 16 maternal uniparental disomy (UPD) and 5 DNA-methylation positive unspecified molecular subtype (PWS Unspec). Literature review informed comparative population frequencies of CYP polymorphisms, phenotypes, and substrate specificity. Among the total PWS cohort, extensive metabolizer (EM) activity prevailed across all cytochromes except CYP1A2, which showed greater ultra-rapid metabolizer (UM) status (p < 0.05), especially among UPD. Among PWS genetic subtypes, there were statistically significant differences in metabolizing status for cytochromes 2D6, 2C19, 2C9, 3A4 and 1A2 acting on substrates such as fluoxetine, risperidone, sertraline, modafinil, aripiprazole, citalopram, and escitalopram. Gonadal steroid therapy may further impact metabolism of 2C19, 2C9, 3A4 and 1A2 substrates. The status of growth hormone treatment may affect CYP3A4 activity with gender specificity. Pharmacogenetic testing together with PWS genetic subtyping may inform psychotropic medication dosing parameters and risk for adverse events.

中文翻译：

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在普拉德-威利综合症患者系列病例中细胞色素P450药物代谢酶的药物遗传学测试

普拉德-威利综合症（PWS）与通常需要使用精神科药物的合并症精神病症状（破坏性行为，焦虑症，情绪障碍和精神病）相关。在此35例PWS患者的临床病例系列中，进行了药物遗传学测试以确定等位基因频率，该频率可预测细胞色素（CYP）P450药物代谢酶2D6、2B6、2C19、2C9、3A4和1A2的活性变化。通过PWS遗传亚型对结果进行鉴定，整理和分析：14个缺失（DEL），16个母体单亲二体性（UPD）和5个DNA甲基化阳性未指定分子亚型（PWS Unspec）。文献综述提供了CYP多态性，表型和底物特异性的比较人群频率。在PWS总人数中，p <0.05），尤其是在UPD中。在PWS遗传亚型中，作用于诸如氟西汀，利培酮，舍曲林，莫达非尼，阿立哌唑，西酞普兰和依他普仑的底物上的细胞色素2D6、2C19、2C9、3A4和1A2的代谢状态在统计学上存在显着差异。性腺类固醇疗法可能会进一步影响2C19、2C9、3A4和1A2底物的代谢。生长激素治疗的状态可能会影响CYP3A4活性，具有性别特异性。药物遗传学测试以及PWS基因分型可能会告知精神药物剂量参数和不良事件的风险。