【摘要】 目的 探讨甲氨蝶呤（MTX）作用通路上6个基因SLCO1B1、SLC19A1、ABCC2、ABCB1、FPGS、GGH的13个相关位点的单核苷酸多态性（SNPs）对原发性中枢神经系统淋巴瘤（PCNSL）患者使用MTX化学治疗4周期疗效的影响。方法 选取复旦大学附属华山医院2017年1月至2021年7月初诊为PCNSL且经4周期疗效评估的患者86例。调取其一般资料、疾病治疗资料、实验室检查结果。采用基质辅助激光解吸电离飞行时间质谱法对患者DNA样本进行分型。采用χ~2检验及多因素Logistic回归分析法分析SNPs对MTX疗效的影响。结果 单因素分析结果显示，rs1045642、rs2032582、rs2305558位点的SNPs对PCNSL患者MTX的疗效有影响（P<0.05）。多元回归分析结果显示，纳入MTX总剂量、性别、年龄、身高等混杂因素后，rs1045642位点SNPs仍对MTX疗效有影响（P<0.05）。结论 ABCB1 rs1045642基因型可作为MTX疗效的独立影响因素，该研究为MTX的临床个体化给药提供了一定依据。更多还原

【Abstract】 Objective To investigate the effect of single nucleotide polymorphisms (SNPs) of 13 loci of 6 genes SLCO1B1,SLC19A1,ABCC2,ABCB1,FPGS and GGH on the efficacy of four cycles of MTX chemotherapy in patients with primary central nervous system lymphoma (PCNSL).Methods Patients who were newly diagnosed with PCNSL and evaluated by four cycles of efficacy in Huashan Hospital,Fudan University were selected as the research subjects from January 2017 to July 2021,and the general data,disease treatment data and laboratory test results were collected.The demographic data and clinical data of 86 patients with PCNSL were obtained from the clinical electronic medical record system.The patient′s DNA samples were typed by matrixassisted laser desorption ionization time of flight mass spectrometry.The effect of SNPs on the efficacy of MTX was analyzed by χ~2 test and multivariate Logistic regression.Results Univariate analysis showed that the SNPs of rs1045642,rs2032582 and rs2305558 had an effect on the efficacy of MTX in patients with PCNSL (P<0.05).Multiple regression analysis showed that rs1045642 still had an effect on the efficacy of MTX (P<0.05) after including confounding factors such as total dose of MTX,gender,age,height.Conclusion ABCB1 rs1045642 genotype can be used as an independent influencing factor of MTX efficacy.This study provides a basis for clinical individualized dosing of MTX.更多还原