Objective  To investigate the correlation and predictive value of GSTP1 and SLCO1B1 gene polymorphism with excretion delay and adverse reactions after high dose methotrexate (HD-MTX) chemotherapy in children with acute lymphoblastic leukemia (ALL).

Methods  80 children with ALL in Children's Hospital Of Nanjing Medical University from January 2021 to December 2022 were collected to detect GSTP1 (rs1695, rs537387344) and SLCO1B1 (rs2306283, rs4149056) gene polymorphism by polymerase chain reaction (PCR). The enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX. At the same time, the adverse reactions in the HD-MTX treatment of all patients were recorded. The correlation among GSTP1 and SLCO1B1 gene polymorphism, excretion delay and adverse reactions of HD-MTX were analyzed by univariate analysis, and the significant factors were found out. The predictive factors were selected and found out through multivariate Logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn to evaluate predictive ability.

Results  There was a correlation between SLCO1B1 rs4149056 TC genotype and excretion delay. The 72 h plasma concentration, GSTP1 rs1695 AA and SLCO1B1 rs4149056 TC genotype also had correlation with adverse reactions of HD-MTX chemotherapy, and the difference is statistically significant (P﹤0.05). The ROC curve analysis results showed that the area under the curve (AUC) of SLCO1B1 rs4149056 TC genotype as the predictor for excretion delay of HD-MTX was 0.618, the AUCs of GSTP1 rs1695 AA and SLCO1B1 rs4149056 TC genotype as predictors for adverse reactions of HD-MTX were 0.623 and 0.729.

Conclusion  SLCO1B1 rs4149056 TC genotype may increase the risk of excretion delay after HD-MTX chemotherapy. GSTP1 rs1695 AA and SLCO1B1 rs4149056 TC genotype may be the risk factors for the adverse reactions of HD-MTX. GSTP1 and SLCO1B1 gene polymorphism are of predictive value for excretion delay and adverse reactions of HD-MTX.

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