CYP3A5(6986A>G)基因多态性与多西他赛不良反应的相关性

Correlation between CYP3A5(6986A>G)Gene Polymorphism and ADRs Caused by Docetaxel

目的:分析细胞色素P_(450)酶(CYP)3A5(6986A>G)基因多态性与多西他赛不良反应(ADR)之间的相关性,为减少多西他赛所致ADR提供有效建议。方法:采用前瞻性队列研究,用焦磷酸测序的方法检测患者的CYP3A5(6986A>G)基因型,建立显性遗传模型,并使用SPSS 20.0评估基因型与该药所致ADR之间的相关性。结果:共纳入117例患者,其中野生型(AA)3例、突变杂合型(AG)30例、突变纯合型(GG)84例。显性遗传模型的统计分析结果显示,CYP3A5(6986A>G)GG组的周围神经毒性和指/趾甲毒性发生率显著高于(AA+AG)组,差异有统计学意义(P<0.05)。结论:CYP3A5(6986A>G)GG基因型显著增加了多西他赛所致周围神经毒性和指/趾甲毒性的发生风险。

OBJECTIVE： To analyze the correlation between CYP3A5 （6986A〉G） gene polymorphism and ADRs caused by docetaxel in order to provide suggestions for reducing the ADR caused by docetaxel. METHODS： In prospective cohort study, pyrosequencing was adopted to detect CYP3A5 genotype （6986A〉G）. Dominant genetic model was established, and the correlation between genotype and ADR caused by docetaxel was evaluated by SPSS 20.0. RESULTS： 117 patients were included. Among them, the number of wild type （AA）, mutation heterozygous type （AG）, mutation homozygous type （GG） was 3, 30 and 84 respectively. Dominant genetic model showed that the incidence of peripheral neurotoxicity and finger/toe nail toxicity in group GG was significantly higher than that of （AA ＋AG） group, with statistical significance （P〈0.05）. CONCLUSIONS： CYP3A5 （6986A〉G） GG genotype significantly increase the incidence of peripheral neurotoxicity and finger/toe nail toxicity caused by docetaxel.