ABCB13435C>T基因多态性对急性淋巴细胞白血病患儿大剂量甲氨蝶呤血药浓度及不良反应的影响

摘要

Objective: To investigate the association between the genetic polymorphism of ABCB1 C3435T 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 C3435T 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 ABCB1 C3435T genotypes and MTX plasma concentration and adverse reactions were investigated.Results: Genetic polymorphism existed at the SNP of ABCB1 C3435T.At the SNP of ABCB1 C3435T, the percentage of CC, CT and TT 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 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 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.%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.