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: Peripheral blood of 132 children with acute lymphoblastic leukemia admitted to the department of pediatric hematology,shengjing hospital affiliated to China medical university from August 2015 to June 2019 was selected to determine the genotype of site 3435 of ABCB1 gene by polymerase chain reaction(PCR)-chip hybridization before receiving high-dose methotrexate treatment.Peripheral blood was collected 48 hours after the start of HD-MTX chemotherapy,and the methotrexate concentration was determined by fluorescence polarization immunoassay.At the same time,the adverse reactions after chemotherapy were observed.Analyze the relationship between the polymorphism of ABCB1 gene and the blood concentration of MTX and adverse reactions after HD-MTX treatment.Results: There was a significant association between the gene polymorphism of site 3435 of ABCB1 gene and the blood concentration of MTX 48 hours after the start of HD-MTX chemotherapy(P<0.05).However,no significant association was found in the polymorphism of ABCB1 C3435 T gene and the adverse reactions generated by HD-MTX chemotherapy(P >0.05).Conclusion: The polymorphism of ABCB1 C3435 T was related to the blood concentration of MTX,but not to adverse reactions(myelosuppression,renal impairment)after high-dose methotrexate chemotherapy in ALL children.