CYP2C19和CYP2J2基因型预测了埃塞俄比亚学龄儿童中普拉齐特血暴露的情况
Tigist Dires Gebreyesus1,2, Eyasu Makonnen3,4, Nigus Fikrie Telele5
1Department of Global Public Health, Karolinska Institutet, Karolinska University Hospital, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
Scientific reports
|May 22, 2024
概括
遗传因素,如CYP2C19和CYP2J2,以及性别,显著影响埃塞俄比亚儿童的PZQ药物水平. 了解这些变异对于优化PZQ治疗以控制杆菌病至关重要.
科学领域:
- 药物遗传学 药物遗传学
- 热带医学 热带医学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 普拉西昆 (PZQ) 是主要用于治疗阴道病的药物.
- 它的新陈代谢受到酶的遗传变异的影响,但这些因素的数据有限.
- 基于学校的大规模药物管理 (MDA) 是控制杆菌病的关键.
研究的目的:
- 研究基因变异 (CYP450酶) 和非遗传因素如何影响埃塞俄比亚学童的PZQ血度和新陈代谢.
- 分析特定CYP基因型 (CYP3A4,CYP3A5,CYP2C19,CYP2C9,CYP2J2) 对PZQ暴露的影响.
- 探索营养状况和共感染对PZQ药理动学的影响.
主要方法:
- 研究了一组446名埃塞俄比亚学龄儿童 (7-15岁),通过MDA接受PZQ和阿尔本达.
- 对CYP2C19,CYP2J2,CYP3A4,CYP3A5和CYP2C9.9的功能变体进行了基因型鉴定.
- 使用UPLC-MS/MS.测量了PZQ及其代谢物 (trans-4-OH-PZQ,cis-4-OH-PZQ) 的度.
主要成果:
- 缺陷的CYP2C19等位基因 (*2, *3) 与更高的PZQ血度有关.
- 携带CYP2C19 (*1/*1, *17) 和CYP2J2*7的携带者表现出变化的代谢比率 (更高的trans-4-OH-PZQ/PZQ和cis-4-OH-PZQ/PZQ).
- 与女性相比,男性参与者具有较高的PZQ水平和较低的代谢比率. 衰老,衰弱和虫感染并没有显著影响PZQ水平.
结论:
- 性别,CYP2C19和CYP2J2基因型是埃塞俄比亚儿童PZQ血暴露的重要预测因素.
- 这些遗传因素在PZQ变异性中起作用,影响其有效性.
- 需要进一步的研究来了解CYP2C19和CYP2J2基因型如何影响PZQ治疗结果.
关键词:
在CYP2C19中.在CYP2J2中.在 CYP3A5A5 中.埃塞俄比亚 埃塞俄比亚 埃塞俄比亚血中的度是什么实际上,这是一个Praziquantel.这种疾病叫做schistosomiasis.更多相关视频
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