摘要
目的:研究急性淋巴细胞白血病(ALL)患儿多药耐药基因1(ABCB1)基因多态性与使用大剂量甲氨蝶呤(MTX)化疗期间的血药浓度及不良反应的关系。方法:70例ALL患儿外周血,提取DNA,采用PCR技术和直接测序的方法分析ABCB1基因的基因型;采用酶放大免疫法(EMIT)测定MTX给药后48h的血药浓度;2.华中科技大学同济医学院同济医院药学部,统计不良反应相关信息。分析ABCB1基因多态性与MTX血药浓度及不良反应的关系。结果:ABCB1 C3435T位点存在多态性,ABCB1 C3435T位点患儿CC、CT和TT基因型的分布频率分别为31.43%,47.14%,21.43%。ABCB1 C3435T位点各基因型MTX 48h C/D值由低到高依次为CC型患儿、CT型患儿、TT型患儿,其中TT型与CC型之间差异具有统计学意义(P<0.05)。ABCB1 C3435T位点不同基因型患者中,口腔黏膜损害、肝脏损害发生率差异有统计学意义(P<0.05)。结论:ABCB1 C3435T位点基因多态性与ALL患儿大剂量MTX化疗后的血药浓度及不良反应(口腔黏膜炎、肝脏损害)有关。
Objective： To investigate the association between the genetic polymorphism of ABCB1 C3435T and plasma concentra- tion and adverse reactions of high-dose methotrexate（HD-MTX） chemotherapy in children with acute lymphoblastie leukemia（ALL）. Methods ： A total of 70 peripheral blood samples were obtained from the children with acute lymphoblastic leukemia for extracting ge- nome DNA. The genetic polymorphism of ABCB1 C3435T locus was examined by using PCR technology and direct sequencing; en- zyme-amplified immunoassay （EMIT） was employed to determine the plasma concentration of MTX in 48 h; the clinical data of patients were collected during the HD-MTX chemotherapy, the adverse reactions were statistically analyzed. The association between ABCB1 C3435T genotypes and MTX plasma concentration and adverse reactions were investigated. Results： Genetic polymoq3hism existed at the SNP of ABCB1 C3435T. At the SNP of ABCB1 C3435T, the percentage of CC, CT and Tr genotype in the children with ALL was 31.43% , 47.14% and 21.43%, respectively. The order of C/D ratio of MTX from low to high was CC, CT and TI＇ genotypes, there was a significant association between the gene polymorphism and the C/D ratio of MTX （P 〈 0.05 ） ; the order of incidence of oral mu- eosa damage from low to high was CC, CT and TY genotypes, there was a significant association between the gene polymorphism and o- ral mucosa damage （ P 〈 0.05 ） ; the order of incidence of hepatotoxicity from low to high were CC, CT and rITE genotypes, the gene pol- ymorphism and hepatotoxicity had a significant association （ P 〈 0.05）. Conclusion ： ABCB1 C3435T genetic polymorphism and C/D ratio of MTX, gastrointestinal side effects and hepatotoxicity after HD-MTX chemotherapy in the children with ALL exhibit significant association.
作者
朱影
楼一层
刘萌萌
王子望
张冲
陈相东
郑恒
Zhu Ying Lou Yiceng Liu Mengmeng Wang Ziwangt zhang Chongt Chen Xiangdong Zheng Heng(School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China Department of Pharmacy,Tongji Hospital Affiliated with Tongji Medical College,Huazhong University of Science and Technology)
出处
《中国药师》
CAS
2017年第6期1058-1061,共4页
China Pharmacist
