Hematotoxicity Correlation of MTHFR Gene Polymorphism with High-dose of Methotrexate in Hematological Neoplasm Patients ：A Meta-analysis
- VernacularTitle:血液恶性肿瘤患者中MTHFR基因多态性与大剂量甲氨蝶呤血液毒性相关性的Meta分析
- Author:
Shuang LIU
1
,
2
,
3
;
Zaiwei SONG
1
,
3
;
Zhanmiao YI
1
,
2
,
3
;
Rongsheng ZHAO
1
Author Information
1. Dept. of Pharmacy，Peking University Third Hospital，Beijing 100191，China
2. Dept. of Pharmacy Administration and Clinical Pharmacy，School of Pharmaceutical Sciences，Peking University，Beijing 100191，China
3. Center for Drug Evaluation，Peking University Health Science Center，Beijing 100191，China
- Publication Type:Journal Article
- Keywords:
Methylenetetrahydrofolate reductase;
Gene polymorphisms;
High-dose methotrexate;
Hematological neoplasms
- From:
China Pharmacy
2020;31(7):850-858
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To systematically evaluate the c orrelation of methylenetetra hydrofolate reductase （MTHFR）C677T and A 1298C gene polymorphisms with blood system adverse events induced by high-dose of methotrexate （HDMTX）. METHODS ： Retrieved from Medline ，Embase，Clinical Trials.gov ，CNKI，Wanfang database ，CBM，cohort studies about MTHFR gene polymorphism in hematological neoplasm treated by HDMTX were collected from inceptions to March 2018. After data extraction of included literatures ，quality evaluation with Newcastle Ottawa scale ，Meta-analysis was performed for adverse events of blood system induced by HDMTX in different genetic models with Rev Man 5.3 software. RESULTS ：Totally 25 cohort studies were included，23 studies of which were related to MTHFR C677T site （including 1 858 patients）and 16 studies related to MTHFR A1298C site （including 1 088 patients）. Results of Meta-analysis showed that MTHFR C677T mutation type significantly increased the risk of hematotoxicity [TT/CT vs. CC ：OR＝1.57，95％CI（1.12，2.20），P＝0.009；TT vs. CT/CC ：OR＝2.19，95％CI（1.49， 3.23），P＜0.001；T vs. C ：OR＝1.34，95％CI（1.03，1.74）， P＝0.03] and severe hematotoxicity [TT/CT vs. CC ：OR＝m 2.33，95％CI（1.43，3.81），P＜0.001]，including leukopenia [TT/CT vs. CC ：OR＝1.37，95％CI（1.02，1.82），P＝0.03]， severe leukopenia [TT/CT vs. CC ：OR＝1.63，95％CI（1.03， 010-82265810。E-mail：zhao_rongsheng@163.com 2.56），P＝0.04]，severe gra nulopenia [TT/CT vs. CC ：OR＝ ·2.26，95％CI（1.50，3.39），P＜0.001]. The mutation genotypes of MTHFR A1298C significantly decreased the risk of severe hematotoxicity [CC/AC vs. AA ：OR＝0.17，95％CI（0.04，0.76），P＝0.02]，including leukopenia [CC/AC vs. AA ：OR＝0.68， 95％CI（0.48，0.97），P＝0.03；CC vs. AC/AA ：OR＝0.28，95％CI（0.14，0.59），P＜0.001] and severe leukopenia [CC/AC vs. AA：OR＝0.43，95％CI（0.19，0.97），P＝0.04]. CONCLUSIONS ：Among patients with hematological neoplasms ，MTHFR C677T mutation may significantly increase the risk of hematotoxicity by HDMTX including the risk of leukopenia and granulopenia ；while MTHFR A1298C may reduce the risk of hematotoxicity by HDMTX ，including the risk of leukopenia.
