骨肉瘤与血液恶性肿瘤患者中甲氨蝶呤药物不良反应的药物遗传学:一项系统评价再评价
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摘要
目的分析基因多态性与甲氨蝶呤(MTX)药物不良反应相关性的系统评价,评价其方法学质量及其结论的可靠程度。方法描述性分析纳入系统评价的基本特征,并用AMSTAR工具评价纳入系统评价的方法学质量,对相关系统评价的结局指标进行数据整合、定性分析和讨论。结果共纳入12项系统评价,10项系统评价分析了MTHFR基因多态性的相关性,2项分析了RFC1基因多态性的相关性,尚无系统评价研究MDR1基因多态性与MTX药物不良反应的相关性。12项系统评价AMSTAR平均得分为7分,其中1项为方法学高质量、其余为方法学中等质量。结论 12篇纳入的系统评价总体方法学质量尚可。MTHFR C677T与MTX药物不良反应(骨髓抑制、肝毒性、胃肠道毒性等)的相关性更大,MTHFR A1298C的相关性相对较小(可能有保护作用),RFC1 G80A的相关性则尚待更多研究验证。
Objective To analyze systematic reviews about pharmacogenetics of methotrexate( MTX)-induced toxicities,evaluate their quality of methodology and evidence. Methods Descriptively analyzed the characteristics of systematic reviews included. Evaluated their methodology quality by AMSTAR. Integrated and qualitatively analyzed outcomes of related systematic reviews. Results Finally 12 systematic reviews were enrolled,in which 10 studies focus on MTHFR polymorphism and 2 on RFC1 and none on MDR1. The average AMSTAR score was 7 points,of which 1 was of high methodology quality and the others were of medium methodology quality. Conclusion The methodology quality of 12 systematic reviews is acceptable. Overall,MTHFR C677 T plays a greater role in increased MTX-induced toxicities,such as myelosuppression,hepatotoxicity and gastrointestinal toxicity. MTHFR A1298 C plays a minor role in decreased MTX-induced toxicities( potential protective effect). The correlation of RFC1 G80 A remains to be verified by more studies.
Objective To analyze systematic reviews about pharmacogenetics of methotrexate( MTX)-induced toxicities,evaluate their quality of methodology and evidence. Methods Descriptively analyzed the characteristics of systematic reviews included. Evaluated their methodology quality by AMSTAR. Integrated and qualitatively analyzed outcomes of related systematic reviews. Results Finally 12 systematic reviews were enrolled,in which 10 studies focus on MTHFR polymorphism and 2 on RFC1 and none on MDR1. The average AMSTAR score was 7 points,of which 1 was of high methodology quality and the others were of medium methodology quality. Conclusion The methodology quality of 12 systematic reviews is acceptable. Overall,MTHFR C677 T plays a greater role in increased MTX-induced toxicities,such as myelosuppression,hepatotoxicity and gastrointestinal toxicity. MTHFR A1298 C plays a minor role in decreased MTX-induced toxicities( potential protective effect). The correlation of RFC1 G80 A remains to be verified by more studies.
引文
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[2]LOPEZ-LOPEZ E,MARTIN-GUERRERO I,BALLESTEROS J,et al.A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia[J].Pharmacogenomics J,2013,13(6):498-506.
[3]刘恩溢,黄琳,赵立波,等.中国人群亚甲基四氢叶酸还原酶C677T多态性与急性淋巴细胞白血病关系的Meta分析[J].中国新药杂志,2012,21(7):808-813.
[4]HAGLEITNER M M,COENEN M J,APLENC R,et al.The role of the MTHFR 677C>T polymorphism in methotrexate-induced liver toxicity:a meta-analysis in patients with cancer[J].Pharmacogenomics J,2014,14(2):115-119.
[5]HE H R,LIU P,HE G H,et al.Association between reduced folate carrier G80A polymorphism and methotrexate toxicity in childhood acute lymphoblastic leukemia:a meta-analysis[J].Leukemia Lymphoma,2014,55(12):2793-2800.
[6]陈洋,夏江宝,何晓东,等.MTHFR基因多态性在MTX治疗急性淋巴细胞白血病过程中毒性反应的Meta分析[J].中华疾病控制杂志,2015,19(8):811-815.
[7]顾平,刘易陇,何霞,等.还原叶酸载体基因多态性与大剂量甲氨蝶呤药物不良反应关系的Meta分析[J].中国临床药理学杂志,2016,32(15):1432-1434.
[8]ZHAO M,LIANG L,JI L,et al.MTHFR gene polymorphisms and methotrexate toxicity in adult patients with hematological malignancies:a meta-analysis[J].Pharmacogenomics,2016,17(9):1005-1017.
[9]黄琳,于芝颖,顾群,等.亚甲基四氢叶酸还原酶基因多态性与甲氨蝶呤不良反应关系的Meta分析[J].中国临床药理学杂志,2016,32(2):183-185.
[10]史天陆,张永煌,李宇,等.亚甲基四氢叶酸还原酶基因C677T和A1298C多态性与甲氨蝶呤致血液系统不良反应关系的Meta分析[J].药物不良反应杂志,2016,18(5):321-329.
[11]ZHU C,LIU Y W,WANG S Z,et al.Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies:a meta-analysis[J].Pharmacogenomics J,2017,18(3):450-459.
[12]朱忱,王晓玲,李晓玲.急性淋巴细胞白血病患儿亚甲基四氢叶酸还原酶(MTHFR)C677T多态性与甲氨蝶呤毒性相关性的Meta分析[J].实用药物与临床,2017,20(9):1009-1014.
[13]徐蕊,王捷,李静,等.大剂量甲氨蝶呤治疗淋巴系统肿瘤的药物不良反应影响因素分析[J].中国临床药理学杂志,2017,33(22):2239-2242.