【摘要】 目的 探讨甲氨蝶呤作用通路上6个相关基因SLCO1B1、SLC19A1、ABCC2、ABCB1、FPGS、GGH的单核苷酸多态性对原发性中枢神经系统淋巴瘤患者使用甲氨蝶呤化疗所致骨髓抑制不良反应的影响。方法 采用基质辅助激光解吸电离飞行时间质谱法对121例原发性中枢神经系统淋巴瘤患者的DNA样本进行基因分型。从电子病历系统获取患者的人口学及相应的临床资料，采用χ2检验及多因素Logistic回归分析探讨单核苷酸多态性对患者化疗后骨髓抑制的影响。结果 121例患者共经历了508个疗程，其中186个疗程（36.6%）发生了骨髓抑制不良反应。单因素分析结果显示，SLCO1B1 rs2306283及GGH rs2305558位点的单核苷酸多态性对甲氨蝶呤所致骨髓抑制的发生率均有影响（P <0.05）。Logistic回归分析显示，SLCO1B1 rs2306283位点单核苷酸多态性仍然对甲氨蝶呤所致骨髓抑制的发生率有影响[OR=1.542,95%CI(1.040,2.287),P=0.031]。结论 SLCO1B1 rs2306283 GG基因型可作为甲氨蝶呤所致骨髓抑制的独立危险因素，为甲氨蝶呤的个体化给药提供依据。更多还原

【Abstract】 Objective To investigate the effect of single nucleotide polymorphisms of six related genes SLCO1B1, SLC19A1, ABCC2, ABCB1, FPGS, and GGH in the pathway of methotrexate(MTX) action on the adverse effects of myelosuppression caused by MTX in patients with primary central nervous system lymphoma(PCNSL). Methods DNA samples from 121 patients with PCNSL were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Patient demographics and corresponding clinical information were obtained from the electronic medical record system. The χ~2 test and multivariate logistic regression analysis were used to explore the effect of single nucleotide polymorphisms on the patients? myelosuppression after chemotherapy, respectively. Results In 121 patients with a total of 508 courses, 186 courses(36.6%) experienced myelosuppressive adverse reactions. Single factor analysis showed that the single nucleotide polymorphisms of SLCO1B1 rs2306283 and GGH rs2305558 had an effect on the incidence of myelosuppression due to MTX(P<0.05).Logistic regression analysis showed that the SNP of SLCO1B1 rs2306283 still had an effect on the incidence of MTX-induced myelosuppression(OR=1.542, 95%CI: 1.040 to 2.287, P=0.031).Conclusion The GG genotype of SLCO1B1 rs2306283 may serve as an independent risk factor for predicting MTX-induced myelosuppression and provide basis for individualized drug therapy of MTX.更多还原