基因变异CYP3A和分类因子诱导的外围神经病变:系统性审查,元分析和候选基因研究
Laurence McEvoy1, Joanne Cliff2, Daniel F Carr1
1Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
Frontiers in pharmacology
|July 20, 2023
概括
糖尿病增加了因纳诱导的周围神经病变 (TIPN) 的风险,这是常见的化疗副作用. 在这项研究中,CYP3A酶的遗传变异没有被发现是TIPN的显著风险因素.
科学领域:
- 药物遗传学 药物遗传学
- 在瘤学瘤学.
- 神经科学是一个神经科学.
背景情况:
- 塔干诱导的外围神经病变 (TIPN) 显著影响癌症治疗的疗效和患者的生活质量.
- 目前对CYP3A家族中的遗传多态性及其与TIPN相关性的研究已经产生了不一致的结果.
研究的目的:
- 系统地审查和元分析CYP3A4*22和CYP3A5*3遗传变异与TIPN之间的关联.
- 在候选基因研究中调查CYP3A4*22,CYP3A5*3基因型/表型和TIPN之间的关系.
主要方法:
- 一项系统性审查确定了12项关于CYP3A4*22,CYP3A5*3和TIPN的药物遗传研究.
- 一项候选基因研究对288名参与者进行了CYP3A4*22和CYP3A5*3的基因定型,评估了代谢器表型.
- 在可能的情况下进行了元分析,以评估基因型和表型与神经毒性的关联.
主要成果:
- 系统性审查发现CYP3A5*3没有一致的关联,CYP3A4*22与TIPN的证据有限.
- 帕克利塔塞尔比多塞塔塞尔更具神经毒性;糖尿病与TIPN发展有显著的关联.
- 候选基因分析和元分析显示,CYP3A变体/表型和TIPN之间没有显著的关联.
结论:
- 糖尿病是Taxane化疗期间发展外围神经病变的重要危险因素.
- CYP3A基因型和代谢物表型似乎不是TIPN的主要风险因素,尽管在没有更大的样本大小的情况下,不能排除微小的贡献.
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