College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Pharmacogenomics. 2020 Aug;21(12):841-851. doi: 10.2217/pgs-2020-0053. Epub 2020 Jul 23.
This study explored whether inherited variants in genes causing the hereditary neuropathy condition Charcot-Marie-Tooth disease are associated with sensitivity to paclitaxel-induced peripheral neuropathy (PN). Hereditary neuropathy genes previously associated with risk of paclitaxel-induced PN were sequenced in paclitaxel-treated patients. Eight putative genetic predictors in five hereditary neuropathy genes (, , , and ) were tested for association with PN sensitivity after accounting for systemic exposure and clinical variables. rs7833751, a proxy for rs7001034, decreased PN sensitivity (additive model, β = -0.41; 95% CI: -0.66 to -0.17; p = 0.0011). None of the other genetic predictors were associated with PN sensitivity. Our results support prior evidence that rs7001034 is protective of PN and may be useful for individualizing paclitaxel treatment to prevent PN.
本研究探讨了导致遗传性周围神经病 Charcot-Marie-Tooth 病的基因中的遗传变异是否与紫杉醇诱导的周围神经病变（PN）的敏感性相关。对接受紫杉醇治疗的患者进行了先前与紫杉醇诱导的 PN 风险相关的遗传性神经病基因测序。在考虑了全身暴露和临床变量后，检测了五个遗传性神经病基因（ ， ， ， 和 ）中的八个假定遗传预测因子与 PN 敏感性的关联。rs7833751 是 rs7001034 的替代物，降低了 PN 的敏感性（加性模型，β=-0.41；95%CI：-0.66 至-0.17；p=0.0011）。其他遗传预测因子均与 PN 敏感性无关。我们的结果支持先前的证据表明 rs7001034 对 PN 具有保护作用，可能有助于个体化紫杉醇治疗以预防 PN。
