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Hematotoxicity Correlation of MTHFR Gene Polymorphism with High-dose of Methotrexate in Hematological Neoplasm Patients :A Meta-analysis / 中国药房
China Pharmacy ; (12): 850-858, 2020.
Article in Chinese | WPRIM | ID: wpr-819100
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.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Observational study / Systematic reviews Language: Chinese Journal: China Pharmacy Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Observational study / Systematic reviews Language: Chinese Journal: China Pharmacy Year: 2020 Type: Article