MTHFR基因多态性与急性淋巴细胞白血病患儿大剂量甲氨蝶呤血药浓度和不良反应的相关性研究  

Study on the relationship between MTHFR polymorphism and high dose methotrexate concentration and adverse reactions in children with acute lymphoblastic leukemia

作　　者：李琰[1] 张文靓[1] 姚敏 吴小林 LI Yan;ZHANG Wen-jing;YAO Min;WU Xiao-lin(Department of Pharmacy,Maternal and Child Health Hospital of Zaozhuang,Zaozhuang 277100,China;Department of Emergency,Maternal and Child Health Hospital of Zaozhuang,Zaozhuang 277100,China)

机构地区：[1]山东省枣庄市妇幼保健院药学部,山东枣庄277100 [2]山东省枣庄市妇幼保健院急诊科,山东枣庄277100

出　　处：《中国药物应用与监测》2022年第1期4-7,共4页Chinese Journal of Drug Application and Monitoring

摘　　要：目的:探讨亚甲基四氢叶酸还原酶(MTHFR)的基因多态性与急性淋巴细胞白血病(ALL)患儿使用大剂量甲氨蝶呤(HD-MTX)化疗期间的血药浓度和不良反应的相关性。方法:采用聚合酶链反应-基因芯片杂交技术检测MTHFR的基因多态性,采用酶放大免疫分析法测定MTX血药浓度,回顾性分析基因多态性与血药浓度和不良反应间的相关性。结果:MTHFRC677TTT型和A1298CCC型患儿在HD-MTX化疗后24、48、72h的血药浓度结果均显著高于CC、CT型(P<0.01)。C677TTT型患儿发生血小板减少、Ⅰ级以上骨髓抑制和Ⅱ级以上白细胞减少的风险较CC型显著增高(P<0.01)。A1298C CC型、AC型患儿发生血小板减少、Ⅰ级以上骨髓抑制的风险较AA型显著增高(P<0.01)。结论:MTHFRC677T和A1298C基因多态性均影响我院ALL患儿使用HD-MTX化疗期间的血药浓度和不良反应。Objective:To investigate the relationship between the methylenetetrahydrofolate reductase(MTHFR)gene polymorphism and high dose methotrexate(HD-MTX)concentration and adverse reactions in children with acute lymphoblastic leukemia(ALL)during the course of chemotherapy.Methods:The MTHFR gene polymorphism was detected by polymerase chain reaction-gene chip hybridization,and the MTX serum concentration was determined by enzyme amplified immunoassay.The correlation between MTHFR gene polymorphism and serum concentration,adverse drug reactions of MTX were analyzed retrospectively.Results:The serum concentration of MTX at 24,48,72 h after HD-MTX chemotherapy in children with MTHFR C677T TT and A1298C CC genotype were significantly higher than those in children with CC and CT genotype(P<0.01).The risk of thrombocytopenia,over gradeⅠmyelosuppression and over gradeⅡleukopenia in children with C677T TT genotype were significantly higher than those in children with CC genotype(P<0.01).The risk of thrombocytopenia and over gradeⅠmyelosuppression in children with A1298C CC and AC genotype were significantly higher than those in children with AA genotype(P<0.01).Conclusion:MTHFR C677T and A1298C gene polymorphisms could affect the serum concentration and adverse drug reactions of children with ALL during the course of HD-MTX chemotherapy.

关 键 词：亚甲基四氢叶酸还原酶 甲氨蝶呤 急性淋巴细胞白血病 基因多态性 

分 类 号：R969.4[医药卫生—药理学] R979.1[医药卫生—药学]