【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。更多还原

【Abstract】 Objective: To investigate the association between the genetic polymorphism of ABCB1 C3435 T and plasma concentration and adverse reactions of high-dose methotrexate( HD-MTX) chemotherapy in children with acute lymphoblastic leukemia( ALL).Methods: A total of 70 peripheral blood samples were obtained from the children with acute lymphoblastic leukemia for extracting genome DNA. The genetic polymorphism of ABCB1 C3435 T locus was examined by using PCR technology and direct sequencing; enzyme-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 ABCB1C3435 T genotypes and MTX plasma concentration and adverse reactions were investigated. Results: Genetic polymorphism existed at the SNP of ABCB1 C3435 T. At the SNP of ABCB1 C3435 T,the percentage of CC,CT and TT genotype in the children with ALL was31. 43%,47. 14% and 21. 43%,respectively. The order of C/D ratio of MTX from low to high was CC,CT and TT 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 mucosa damage from low to high was CC,CT and TT genotypes,there was a significant association between the gene polymorphism and oral mucosa damage( P < 0. 05); the order of incidence of hepatotoxicity from low to high were CC,CT and TT genotypes,the gene polymorphism and hepatotoxicity had a significant association( P < 0. 05). Conclusion: ABCB1 C3435 T 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.更多还原