儿童急性淋巴细胞白血病中ABCB1C3435T位点基因多态性对大剂量甲氨蝶呤血药浓度及不良反应的影响

目的 研究急性淋巴细胞白血病(ALL)儿童的ABCB1 C3435T位点(rs1045642)基因多态性与大剂量甲氨蝶呤(HD-MTX)化学治疗后血浆中甲氨蝶呤血药浓度和不良反应的相关性.方法 选取2015年8月至2019年6月于我院小儿血液内科住院治疗的132例ALL患儿,在接受HD-MTX治疗前应用聚合酶链反应(P...

Effect of of ABCB1 C3435T gene polymorphism on plasma concentration and adverse reactions of high-dose methotrexate in children with acute lymphoblastic leukemia

Objective To investigate the correlation between ABCB1 C3435T(rs1045642)gene polymorphism in children with acute lymphoblastic leukemia(ALL)and plasma concentration of methotrexate and adverse reactions after high-dose methotrexate(HD-MTX)chemotherapy.Methods Seripheral blood of 132 children with ALL admitted to the Department of Pediatric Hematology of our hospital from August 2015 to June 2019 was collected to determine the genotype of site 3435 of ABCB1 gene by polymerase chain reaction(PCR)-chip hybridization before receiving HD-MTX treatment.Peripheral blood was collected 48 hours after HD-MTX treatment,and the plasma methotrexate concentration was determined by fluorescence polarization immunoassay.At the same time,the adverse reactions after chemotherapy were observed.The relationship of polymorphism of ABCB1 gene with the blood concentration of MTX and adverse reactions were analyzed after HD-MTX treatment.Results There was a significant association between gene polymorphism of site 3435 of ABCB1 gene and blood concentration of MTX at 48 hours after HD-MTX chemotherapy(P<0.05),children with TT genotype had higher MTX plasma concentration 48 h after chemotherapy.However,no correlation was found between the polymorphism of ABCB1 C3435T gene and the adverse reactions of HD-MTX chemotherapy(P>0.05).Conclusion The polymorphism of ABCB1 C3435T is related to the blood concentration of MTX,but not to adverse reactions(myelosuppression,renal impairment)after high-dose methotrexate chemotherapy in ALL children.