急性淋巴细胞白血病患儿MTHFR基因多态性与大剂量甲氨蝶呤毒副反应的关系

doi:10.7499/j.issn.1008-8830.2013.03.009

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摘要目的：探讨亚甲基四氢叶酸还原酶（MTHFR）基因单核苷酸多态性对急性淋巴细胞白血病（ALL）患儿使用大剂量甲氨蝶呤（HD-MTX）化疗后毒副反应的影响。方法：应用RT-PCR-变性梯度凝胶电泳结合DNA测序技术，对52例ALL患儿MTHFR C677T、A1298C和G1793A基因型进行检测。按照国立癌症研究所常规毒性判定标准（NCI-CTC）对患儿HD-MTX化疗后的不良反应统一评价。结果：MTHFR 1298AC基因型患儿发生血小板减少的风险较AA型提高了13.7倍（OR=13.7，95%CI=1.18～159.36，P=0.036）。MTHFR C677T和G1793A各基因型发生各类HD-MTX化疗不良反应的差异无统计学意义（P>0.05）。结论：MTHFR A1298C多态性可能与ALL患儿HD-MTX化疗后的毒副反应相关。

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	郑苗苗
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	丁慧

关键词 ：亚甲基四氢叶酸还原酶, 单核苷酸多态性, 急性淋巴细胞白血病, 甲氨蝶呤, 毒副反应, 儿童

Abstract：OBJECTIVE: To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL). METHODS: MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). RESULTS: The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes. CONCLUSIONS: MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.

Key words： Methylenetetrahydrofolate reductase Single nucleotide polymorphism Acute lymphoblastic leukemia Methotrexate Adverse reaction Child

引用本文:

郑苗苗,岳丽杰,陈小文等. 急性淋巴细胞白血病患儿MTHFR基因多态性与大剂量甲氨蝶呤毒副反应的关系[J]. 中国当代儿科杂志, 2013, 15(3): 201-206.

ZHENG Miao-Miao,YUE Li-Jie,CHEN Xiao-Wen et al. Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia[J]. CJCP, 2013, 15(3): 201-206.

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http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2013.03.009 或 http://www.zgddek.com/CN/Y2013/V15/I3/201

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