Effect of ABCB13435C>T Genetic Polymorphism on Plasma Concentration and Adverse Reactions of High-dose Methotrexate in Acute Lymphoblastic Leukemia Children / 中国药师

ABSTRACT

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.