胃癌晚期患者CYP3A5^(*)3基因多态性与阿帕替尼单药治疗不良反应的相关性研究  

Correlation between CYP3A5^(*)3 Gene Polymorphism and Adverse Reactions of Apatinib Monotherapy in Patients with Advanced Gastric Cancer

作　　者：孟安娜 李杨[1] MENG Anna;LI Yang(Department of Pharmacy,Nanjing Hospital Affiliated to Nanjing Medical University/Nanjing First Hospital,Nanjing 210006,China)

机构地区：[1]南京医科大学附属南京医院/南京市第一医院药学部,南京210006

出　　处：《现代检验医学杂志》2024年第1期1-4,105,共5页Journal of Modern Laboratory Medicine

基　　金：江苏省南京药学会常州四药医院药学科研项目(NO.2019YX013):CYP3A4^(*)1G/18B及CYP3A5^(*)3基因多态性对晚期胃癌患者阿帕替尼稳态血药浓度及不良反应影响的研究。

摘　　要：目的探讨胃癌晚期患者细胞色素P4503A5^(*)3(CYP3A5^(*)3)基因多态性与阿帕替尼单药治疗不良反应的关系。方法选取南京市第一医院2020年1月~2022年6月接受阿帕替尼单药治疗的胃癌晚期患者86例。采集患者2ml外周静脉血,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)联合测序法鉴定患者CYP3A5^(*)3的基因型,分析其与阿帕替尼所致不良反应的相关性。结果86例患者中,突变杂合子型(AG型)29例,突变纯合子型(GG型)51例,突变型占比93.02%。携带CYP3A5^(*)3 GG基因型的患者高血压和白细胞减少的发生率明显高于AA+AG基因型患者(χ^(2)=6.154,6.947,P=0.043,0.027)。阿帕替尼治疗相关的其他不良反应未发现与CYP3A5^(*)3基因型的相关性(P>0.05)。此外,未发现CYP3A5^(*)3基因型与严重不良反应的相关性(P>0.05)。结论CYP3A5^(*)3 GG基因型明显增加阿帕替尼单药治疗所致的高血压和白细胞减少发生风险,未发现其与严重不良反应发生风险的相关性。Objective To investigate the relationship between cytochrome P4503A5^(*)3(CYP3A5^(*)3)gene polymorphism and adverse reactions of apatinib monotherapy in advanced gastric cancer patients.Methods A total of 86 patients with advanced gastric cancer who received apatinib monotherapy at Nanjing First Hospital from January 2020 to June 2022 were selected,and 2 ml of peripheral venous blood from patients was collected.The genotype of CYP3A5^(*)3 was identified using PCR-RFLP combined sequencing method,and its correlation with adverse reactions was analyzed by apatinib.Results Among the 86 patients,there were 29 cases of mutant heterozygous genotype(AG genotype)and 51 cases of mutant homozygous genotype(GG genotype),with a mutation type accounting for 93.02%.The incidence of hypertension and leukopenia in patients with the CYP3A5^(*)3 GG genotype was significantly higher than in patients with the AA+AG genotype(χ^(2)=6.154,6.947,P=0.043,0.027).Other adverse reactions related to apatinib treatment were not found to be associated with the CYP3A5^(*)3 genotype(P>0.05).In addition,no correlation was found between severe adverse reactions and the CYP3A5^(*)3 genotype(P>0.05).Conclusion The CYP3A5^(*)3 GG genotype significantly increased the risk of hypertension and leukopenia caused by apatinib monotherapy,and no correlation was found with the risk of serious adverse reactions.

关 键 词：细胞色素P4503A5^(*)3 基因多态性 胃癌 阿帕替尼 不良反应 

分 类 号：R735.2[医药卫生—肿瘤] R730.43[医药卫生—临床医学]