在疑似药物诱导的间歇性肺病患者中,药物基因风险分层
Marjolein Drent1,2,3, Petal A Wijnen4,5,6, Naomi T Jessurun5,7
1Department of Pharmacology and Toxicology, Faculty of Health, Medicine, and Life Science, Maastricht University, Maastricht, The Netherlands. m.drent@ildcare.nl.
Drug safety
|March 9, 2024
概括
药物代谢酶的遗传变异与药物诱导的间歇性肺病 (DI-ILD) 有关. 了解这些遗传因素对于诊断和管理纤维化肺部疾病至关重要.
科学领域:
- 药物基因组学 药物基因组学
- 肺部医学 肺部医学
- 毒理学 毒理学 毒理学
背景情况:
- 肺毒性是药物使用的一个未被认可的并发症.
- 药物诱导的间歇性肺病 (DI-ILD) 是一个诊断挑战.
- 遗传因素可能会影响易受DI-ILD的易感性.
研究的目的:
- 调查细胞染色体P450 (CYP) 酶中的遗传多态化与DI-ILD之间的关联.
- 为了确定特定的CYP基因变异是否与因药物暴露而患有纤维性肺病的风险相关.
主要方法:
- 对467名怀疑DI-ILD的患者进行了回顾性观察性研究.
- 分析CYP2D6,CYP2C9和CYP2C19异酶中的遗传变异.
- 遗传发现与药物使用模式和临床诊断的相关性 (非特异性间歇性肺炎,异常性肺纤维化).
主要成果:
- 79%的患者表现出与药物代谢相关的基因多态性.
- 60%被归类为可能的DI-ILD (代谢不良或多药性).
- 37.5%被归类为极有可能的DI-ILD.
- 类药物是最常用的药物,特别是在男性中.
结论:
- 怀疑DI-ILD的患者中有很大一部分携带影响药物代谢的遗传变异.
- 与药物史结合的CYP遗传分析有助于诊断DI-ILD.
- 遗传倾向和药物暴露是纤维化肺部疾病发展和进展的关键因素.
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