GSTP1和SLCO1B1基因多态性对大剂量甲氨蝶呤化疗排泄延迟及不良反应的影响

Effect of GSTP1 and SLCO1B1 gene polymorphism on excretion delay and adverse reactions after high dose methotrexate chemotherapy

目的 研究GSTP1和SLCO1B1基因多态性与儿童急性淋巴细胞白血病(ALL)患儿使用大剂量甲氨蝶呤(HD-MTX)化疗后出现排泄延迟及不良反应的相关性及预测价值。方法 选择2021年1月至2022年12月南京医科大学附属儿童医院80例ALL患儿为研究对象,采用聚合酶链式反应(PCR)法测定所有患儿GSTP1(rs1695、rs537387344)和SLCO1B1(rs2306283、rs4149056)等位点的基因多态性,采用均相酶扩大免疫分析(EMIT)法测定MTX血药浓度,记录在接受HD-MTX治疗过程中发生的不良反应。用单因素分析GSTP1和SLCO1B1基因多态性、HD-MTX排泄延迟及不良反应的相关性,并得出显著性因素;用多因素Logistic回归筛选出预测因子,绘制受试者工作特征(ROC)曲线评价预测价值。结果 SLCO1B1 rs4149056 TC与排泄延迟具有相关性;72 h血药浓度、GSTP1 rs1695 AA、SLCO1B1 rs4149056 TC基因型与MTX化疗后不良反应的发生具有相关性,差异有统计学意义(P <0.05)。ROC曲线分析结果表明,SLCO1B1 rs4149056 TC预测HD-MTX排泄延迟的曲线下面积(AUC)为0.618,GSTP1 rs1695 AA与SLCO1B1 rs4149056 TC预测HD-MTX不良反应的AUC分别为0.623和0.704。结论 SLCO1B1 rs4149056 TC基因型可能增加HD-MTX化疗后发生排泄延迟的风险,GSTP1 rs1695 AA、SLCO1B1 rs4149056 TC基因型可能是发生不良反应的危险因素。SLCO1B1基因多态性对HD-MTX化疗后排泄延迟和不良反应具有一定的预测价值。

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.