评估甲铁酸的药物基因组变异,以预测患有急性淋巴细胞白血病的儿童急性神经毒性
Rachel D Harris1,2,3,4, Olga A Taylor1,2,3, M Monica Gramatges1,2
1Texas Children's Cancer and Hematology Centers, Houston, Texas, USA.
Pharmacotherapy
|December 30, 2024
概括
甲铁酸的基因变异药基因组学显示,在患有急性淋巴细胞白血病 (ALL) 的儿童中,与神经毒性存在适度的关联. 这些变体并没有显著改善与甲状腺素相关的神经毒性风险预测.
科学领域:
- 药物基因组学 药物基因组学
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
背景情况:
- 甲索酸对于儿童急性淋巴细胞白血病 (ALL) 治愈疗法至关重要.
- 在ALL患者中影响甲状腺的代谢和运输的遗传因素尚不清楚.
- 这项研究调查了药物基因组变异与儿科ALL中甲状腺素诱导的神经毒性之间的联系.
研究的目的:
- 评估特定的甲状腺素药物基因组变异与ALL儿童神经毒性风险之间的关联.
- 为了确定这些遗传变异是否可以改善这种患者群体中神经毒性的预测.
主要方法:
- 包括763名儿童 (年龄在2-20岁),在2005-2019年期间接受了ALL治疗.
- 在21天内对神经毒性事件进行了审查.
- 用后勤回归和随机森林模型对97种甲状腺素药物基因组变异进行基因定型和评估关联.
主要成果:
- 8.2%的患者出现了与甲状腺素相关的神经毒性.
- 在调整后的模型中,没有药物基因组变异达到统计学意义.
- 两个变体 (ABCC2中的rs17222723和ABCB1中的rs1045642) 显示了与神经毒性 (p <0.05) 的名义关联.
- 药物基因组变异没有提高随机森林神经毒性模型的预测性能.
结论:
- 在儿科ALL中,甲状腺素的药物基因组变异和神经毒性易感性之间的关联通常很小.
- 这些变体并没有显著改善ALL儿童中甲铁酸相关神经毒性风险分层.
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