探索性聚焦的药物遗传测试揭示了与沙特自闭症儿童里斯佩里药物动力学相关的新型标记物
Sireen Abdul Rahim Shilbayeh1, Iman Sharaf Adeen2, Ezzeldeen Hasan Ghanem3
1Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Frontiers in pharmacology
|February 20, 2024
概括
这项研究确定了影响自闭症谱系障碍 (ASD) 儿童RIS药物暴露的新型药物遗传学 (PGx) 标志物. 这些发现可能有助于个性化抗精神病治疗ASD.
科学领域:
- 药物基因组学 药物基因组学
- 神经发育障碍 神经发育障碍
- 药物新陈代谢 药物新陈代谢
背景情况:
- 自闭症谱系障碍 (ASD) 呈现出多种表型,具有潜在的神经变化.
- 基因组研究表明,ASD病因和影响药物药理动力学 (PK) 和药理动力学 (PD) 的基因之间存在重叠.
- 目前用于ASD抗精神病剂量的药物遗传学 (PGx) 标记物的应用是有限的,这是由于相互矛盾的数据和非标签药物使用.
研究的目的:
- 确定PGx标志物,预测沙特儿童患有自闭症的RIS暴露.
- 探索超越经典RIS PK路径的新型遗传关联.
主要方法:
- 对89名沙特儿童进行前性队列研究,这些儿童患有ASD并接受RIS治疗.
- 通过液体染色学-并联质谱法量化RIS和9-OH-RIS血水平.
- 用Axiom PharmacoFocus Array进行协会分析,对720个PGx标记物的基因定型.
主要成果:
- 27个PGx变种对RISPK参数产生了显著的影响,其中许多在经典RISP路径之外.
- 7个基因中的8个标志物显示出与RIS水平的最强相关性 (p < 0.01).
- 与UGT2B17 (rs78998153) 和人类白细胞抗原 (HLA) 标记物发现的新关联影响了RIS暴露.
结论:
- 广泛的PGx标记物相互作用,影响ASD儿童的RIS暴露.
- 结果表明需要在人群PK建模中进行验证,以开发个性化抗精神病治疗的多基因分数.
- 这项研究支持自闭症管理的个性化治疗决策.
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