MTHFD1及FPGS和GGH基因多态性对大剂量甲氨蝶呤中枢疗效的影响

Effect of Genetic Polymorphisms of MTHFD1,FPGS,GGH on the Efficacy of High Dose Methotrexate

目的探讨亚甲基四氢叶酸脱氢酶(MTHFD1)、叶酰多聚谷氨酸合成酶(FPGS)和γ-谷氨酰水解酶(GGH)的基因多态性与大剂量甲氨蝶呤(HD-MTX)对非霍奇金淋巴瘤(NHL)患者中枢治疗效果之间的相关性。方法接受HD-MTX化疗的原发中枢或中枢转移的NHL患者共71例,用Sequenom MassARRAY时间飞行质谱检测MTHFD1、FPGS和GGH的基因型分布情况,根据卢加诺缓解标准评价用药后的中枢治疗效果,用SPSS 22.0版软件分析MTHFD1、FPGS和GGH基因型对疗效的影响。结果MTHFD1 rs2236225基因分型与疗效之间有显著相关性(P=0.011),FPGS rs10106和GGH rs1800909基因多态性对疗效无影响(P>0.05);纳入年龄、性别、疾病分期、MTX剂量等因素进行多元回归分析后,MTHFD1 rs2236225基因分型与疗效仍有显著相关性(P=0.023)。结论MTHFD1的基因多态性可能影响MTX的中枢治疗效果,需要进一步扩大样本确定;未观察到FPGS、GGH基因多态性与MTX疗效之间有明显的相关性。

Objective To investigate the association of genetic polymorphisms of MTHFD1,FPGS and GGH with the efficacy of high dose methotrexate(HD-MTX)in patients with non-Hodgkin lymphoma(NHL).Methods Seventy-one patients with primary central nervous system lymphoma(PCNSL)or with NHL metastasis to central nervous system were enrolled in this study.The polymorphisms of MTHFD1 rs2236225,FPGS rs10106 and GGH rs1800909 were genotyped using the Sequenom MassARRAY technology platform.The outcome of HD-MTX was evaluated by Lugano response criteria and the association with the genetic polymorphisms was statically analyzed by SPSS 22.0.Results The genotype of MTHFD1 rs2236225 was associated with the efficacy of HD-MTX(P=0.011).After adjusting for age,gender,disease stage,dosage and therapy method,MTHFD1 rs2236225 remained significantly associated with the efficacy(P=0.023).Conclusion The gene polymorphism of MTHFD1 may affect the efficacy of MTX in patients with NHL,however,there is no association with FPGS,GGH and the efficacy of MTX.