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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 relationship between the polymorphism of multidrug resistance gene 1 (ABCB1) gene in children with acute lymphoblastic leukemia (ALL) and the blood concentration and side effects during high dose methotrexate (MTX) chemotherapy. Methods: The genotypes of ABCB1 gene were analyzed by PCR and direct sequencing in peripheral blood of 70 ALL children. The genotypes of ABCB1 gene were determined by enzyme-linked immunosorbent assay (EMIT) Department of Pharmacy, Tongji Hospital, Tongji Medical College, Tongji Medical College, Statistical Information on Adverse Events. The relationship between ABCB1 gene polymorphism and MTX plasma concentration and adverse reactions was analyzed. Results: The polymorphisms of ABCB1 C3435T locus were found. The frequencies of CC, CT and TT genotypes in children with ABCB1 C3435T were 31.43%, 47.14% and 21.43%, respectively. The genotypes of ABCB1 C3435T genotype MTX 48h C / D values from low to high were CC type children, CT type children, TT type children, TT type and CC type difference was statistically significant (P < 0.05). There were significant differences in the incidence of oral mucosal damage and liver damage among ABCB1 C3435T genotypes (P <0.05). Conclusion: ABCB1 C3435T gene polymorphism is associated with plasma concentration and adverse reactions (oral mucositis and liver damage) after high dose MTX chemotherapy in children with ALL.