MTHFR和ABCB1基因多态性对血液恶性肿瘤患者甲氨蝶呤血药浓度和不良反应的影响  

Effects of polymorphisms of MTHFR and ABCB1 on serum concentration and adverse reactions of methotrexate in patients with hematological malignancies

作　　者：蒋艳[1] 胡楠[1] 凌静[1] 杨旭萍 邹素兰[1] 贺煜添 董露露 JIANG Yan;HU Nan;LING Jing;YANG Xuping;ZOU Sulan;HE Yutian;DONG Lulu(The First People's Hospital of Changzhou,Changzhou 213000,China;Xuzhou Medical University,Xuzhou 221000,China)

机构地区：[1]常州市第一人民医院,江苏常州213000 [2]徐州医科大学,江苏徐州221000

出　　处：《临床医药实践》2025年第5期358-362,共5页Proceeding of Clinical Medicine

摘　　要：目的:探讨亚甲基四氢叶酸还原酶(MTHFR)和三磷酸腺苷结合盒转运体亚家族B成员1(ABCB1)基因多态性对大剂量甲氨蝶呤(MTX)治疗血液恶性肿瘤患者血药浓度和不良反应的影响。方法:选择2020年7月—2021年12月在常州市第一人民医院血液科就诊的42例血液恶性肿瘤患者。采用荧光染色原位杂交法测定MTHFR(677 C>T),MTHFR(1298 A>C),ABCB1(3435 C>T)分型,收集患者MTX血药浓度监测结果及用药期间相关临床资料,分析MTHFR和ABCB1基因多态性与MTX血药浓度及不良反应的关系。结果:MTHFR(677 C>T)中各基因型24 h,48 h,72 h的MTX血药浓度比较,差异均无统计学意义(P>0.05)。MTHFR(1298 A>C)不同基因型MTX用药后AC+CC型24 h血药浓度显著高于AA型(P<0.05),而ABCB1(3435 C>T)纯合突变TT型24 h血药浓度显著高于CC型和CT型,TT型患者48 h MTX血药浓度显著高于CT型患者;MTHFR(677 C>T)不同基因型患者不良反应发生风险比较,差异无统计学意义(P>0.05),而MTHFR(1298 A>C)与ABCB1(3435 C>T)与患者部分不良反应发生风险相关,差异有统计学意义(P<0.05)。结论:MTHFR(1298 A>C)和ABCB1(3435 C>T)基因多态性与HD-MTX化疗后患者的MTX血药浓度及部分不良反应的发生显著相关,可用于指导血液肿瘤患者的临床个体化用药治疗。Objective:To investigate the effects of methylenetetrahydrofolate reductase(MTHFR)and ATP binding cassette transporter(ABC)gene polymorphisms on the serum concentration and adverse reactions of high-dose methotrexate(MTX)in the treatment of hematological malignancies.Methods:A total of 42 patients with hematological malignancies who were admitted to the First People's Hospital of Changzhou from July 2020 to December 2021 were selected.Fluorescence in situ hybridization was used to determine the type of MTHFR 677(677 C>T),MTHFR 1298(1298 A>C),ABCB1(3435 C>T)and blood concentration information and clinical data during medication were collected.The correlation between MTHFR and ABCB1 gene polymorphism and MTX plasma concentration and adverse reactions was analyzed.Results:There were no significant differences in the plasma concentrations of MTHFR(677 C>T)at 24 h,48 h,and 72 h(P>0.05).The 24-hour plasma concentrations of AC+CC type of MTHFR(1298 A>C)were significantly higher than those of AA type(P<0.05),while the 24-hour plasma concentrations of ABCB1(3435 C>T)homozygous mutant TT type were significantly higher than those of CC type and CT type,and the blood concentration of TT type 48hMTX was significantly higher than that of CT type(P<0.05).There was no significant difference in the risk of adverse reactions among patients with different genotypes of MTHFR(677 C>T),while MTHFR(1298 A>C)and ABCB1(3435 C>T)were associated with the risk of some adverse reactions(P<0.05).Conclusion:MTHFR(1298 A>C)and ABCB1(3435 C>T)gene polymorphisms are significantly correlated with MTX plasma concentration and some adverse reactions after HD-MTX chemotherapy,which can be used to guide the individualized therapy of patients with hematological tumors.

关 键 词：甲氨蝶呤 基因多态性 血液恶性肿瘤 个体化治疗 

分 类 号：R969.3[医药卫生—药理学]