MTHFR及ABCB1基因多态性与急性淋巴细胞白血病患儿大剂量甲氨蝶呤药物不良反应关系
Retrospective cohort study on the relationship between MTHFR and ABCB1 gene polymorphisms and high-dose methotrexate toxicity in children with acute lymphoblastic leukemia
徐蕊 1李静 2胡玉 1麦吾菊丹·阿力甫 1张瑞 1姜雯 1孙璇 1王琳 3赵军4
作者信息
- 1. 新疆医科大学第六附属医院药学部,新疆维吾尔自治区乌鲁木齐 830002
- 2. 新疆医科大学 第一附属医院 药学部,新疆维吾尔自治区乌鲁木齐 830054
- 3. 新疆医科大学第六附属医院全科医学科,新疆维吾尔自治区乌鲁木齐 830002
- 4. 新疆医科大学 第一附属医院 药学部,新疆维吾尔自治区乌鲁木齐 830054;新疆药物临床研究重点实验室,新疆维吾尔自治区乌鲁木齐 830054
- 折叠
摘要
目的 确定亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C及多药耐药1(ABCB1)C3435 T基因多态性与急性淋巴细胞白血病(ALL)患儿大剂量甲氨蝶呤(HD-MTX)药物不良反应关系.方法 收集用HD-MTX化疗的ALL患儿血样,用测序法检测MTHFR C677T、A1298C和ABCB1 C3435T基因多态性,根据抗癌药物常见药物不良反应分级标准统一评价MTX化疗后的药物不良反应,统计分析MTHFR C677T、A1298C及ABCB1 C3435T基因多态性与HD-MTX药物不良反应的关系.结果 MTHFR A1298C AC+CC型肝功能损伤(2级)风险高于 AA 型[比值比(OR)=2.350,95％置信区间(CI)=1.038～5.320,P＜0.05)],未发现MTHFR A1298C与骨髓抑制、黏膜损伤、胃肠道反应及急性肾损伤有相关性(均P＞0.05).ABCB1 C3435TCT型肝功能损伤(2级)风险高于 TT 型(OR 5.161,95％CI=1.371～19.424,P＜0.05),ABCB1 C3435TCC+CT型肝功能损伤(2级)风险高于TT型(OR 4.231,95％CI=1.165～15.362,P＜0.05),未发现ABCB1 C3435T与骨髓抑制、黏膜损伤、胃肠道反应及急性肾损伤有相关性(均P＞0.05).未发现MTHFR C677T与HD-MTX药物不良反应有相关性(均P＞0.05).结论 在用HD-MTX治疗ALL时,可通过检测MTHFR A1298C及ABCB1 C3435T基因型来预测药物不良反应,从而实施更加科学的个体化用药.
Abstract
Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.
关键词
急性淋巴细胞白血病/儿童/大剂量甲氨蝶呤/亚甲基四氢叶酸还原酶/多药耐药1/药物不良反应Key words
acute lymphoblastic leukemia/children/high dose methotrexate/methylenetetrahydrofolate reductase/multidrug resistance 1/adverse drug reaction引用本文复制引用
基金项目
国家重点研发计划课题基金资助项目(2017YFC0910001)
天山英才医药卫生高层次人才培养计划基金资助项目(TSYC202301A051)
新疆医科大学第六附属医院临床药学重点专科基金资助项目(202401)
出版年
2024
国家科技期刊平台
NSTL
万方数据