MTHFR基因多态性与急性淋巴细胞白血病患儿甲氨蝶呤化疗后不良反应及临床预后的关系  

Relationships of MTHFR gene polymorphisms with adverse reactions and clinical prognosis of acute lymphoblastic leukemia children after methotrexate chemotherapy

作　　者：郑明霞 赵文理[3] ZHENG Mingxia;ZHAO Wenli(Clinical College of Pediatrics,Medical Department of Soochow University,Suzhou 215000,China)

机构地区：[1]苏州大学医学部儿科临床医学院,江苏苏州215000 [2]苏州大学附属儿童医院 [3]上海交通大学附属第六人民医院南院

出　　处：《山东医药》2020年第4期26-29,共4页Shandong Medical Journal

基　　金：上海市卫计委科研课题(20164124)

摘　　要：目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与急性淋巴细胞白血病(ALL)患儿甲氨蝶呤(MTX)化疗后不良反应和临床预后的关系。方法选取拟行大剂量MTX化疗的ALL患儿112例,治疗前抽取患儿空腹外周静脉血,应用聚合酶链式反应(PCR)-限制性片段长度多态性分析(RFLP)对患儿MTHFR基因的C 677 T和A 1298 C基因型进行检测,统计学分析各基因型患儿与治疗后不良反应及临床预后的关系。结果112例ALL患儿中,MTHFR基因C 677 T位点中CT型占44.6%,MTHFR基因A 1298 C位点中AA型占53.5%。MTHFR C 677 T各基因型患儿在胃肠道反应、骨髓抑制、皮肤黏膜损伤及肝肾功能损害间差异无统计学意义(P均>0.05),MTHFR A 1298 C各基因型患儿在胃肠道反应间差异有统计学意义(P均<0.05),而在骨髓抑制、皮肤黏膜损伤及肝肾功能损害间差异无统计学意义(P均>0.05)。MTHFR C 677 T基因型中TT型患儿复发率高于CC、CT型患儿(P均>0.05),TT型ALL患儿无事件生存期(EFI)较CC型、CT型患儿长(P均<0.05)。MTHFR A 1298 C基因型中CC、AA、AC基因型患儿复发率比较差异无统计学意义(χ^2=0.173,P=0.917)。CC、AA、AC基因型患儿EFI比较差异无统计学意义(F=3.03,P=0.052)。结论MTHFR基因多态性与ALL患儿MTX化疗后不良反应及临床预后有关。Objective To study the relationships of methotrexate reductase(MTHFR)gene polymorphisms with adverse reactions and clinical prognosis of children with acute lymphoblastic leukemia(ALL)after methotrexate(MTX)chemotherapy.Methods A total of 112 children with ALL who received high-dose MTX chemotherapy were selected,and C 677 T and A 1298 C genotypes of MTHFR gene in peripheral blood samples of 112 children with ALL before treatment were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).The relationships of different genotypes of children with the adverse reactions and clinical prognosis was statistically analyzed.Results The MTHFR C 677 T CT genotype accounted for 44.6%,and the MTHFR A 1298 C AA genotype accounted for 53.5%.MTHFR C 677 T genotypes had no significant difference in gastrointestinal reactions,myelosuppression,skin mucosal damage,or liver and kidney function damage(all P>0.05).MTHFR A 1298 C genotypes had significant differences in gastrointestinal reactions(P<0.05),but there were no significant differences in myelosuppression,skin mucosal injury or liver and kidney function damage(all P>0.05).The recurrence rate of children with TT type of MTHFR C 677 T was significantly lower than that of children with CC and CT types(χ^2=0.392,0.758,P=0.531,and 0.384).The EFI of children with TT type was significantly longer than that of children with CC type and CT types(t=3.534,2.322,P=0.001,0.023).There was no significant difference in the recurrence rates between children with CC,AA,and AC genotypes of MTHFR A 1298 C(χ^2=0.173,P=0.917).There was no significant difference in EFI between children with CC,AA and AC genotypes(F=3.03,P=0.052).Conclusion The MTHFR gene polymorphisms are associated with adverse reaction and clinical prognosis in children after MTX chemotherapy.

关 键 词：急性淋巴细胞白血病 亚甲基四氢叶酸还原酶 甲氨蝶呤 不良反应 预后 

分 类 号：R552[医药卫生—血液循环系统疾病]