Department of Genetics, Physic Anthropology and Animal Physiology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Spain.
Pharmacogenomics J. 2013 Dec;13(6):498-506. doi: 10.1038/tpj.2012.44. Epub 2012 Oct 23.
Methotrexate (MTX) is an important component of therapy used to treat childhood acute lymphoblastic leukemia (ALL). Two single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect MTHFR activity. A large body of studies has investigated the potential role of MTHFR SNPs in MTX toxicity in pediatric ALL. However, the results are controversial. In this review and meta-analysis, we critically evaluate the relationship between the C677T and A1298C polymorphisms of MTHFR and MTX toxicity in pediatric ALL. The majority of published reports do not find associations between MTHFR polymorphisms and toxicity in pediatric ALL. When associations are reported, often the results are contradictory to each other. The meta-analysis confirms a lack of association. In conclusion, MTHFR, C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity in pediatric ALL.
甲氨蝶呤（MTX）是治疗儿童急性淋巴细胞白血病（ALL）的重要组成部分。亚甲基四氢叶酸还原酶（MTHFR）基因中的两个单核苷酸多态性（SNP），C677T 和 A1298C，影响 MTHFR 活性。大量研究探讨了 MTHFR SNP 在儿童 ALL 中 MTX 毒性的潜在作用。然而，结果存在争议。在本综述和荟萃分析中，我们批判性地评估了 MTHFR 的 C677T 和 A1298C 多态性与儿童 ALL 中 MTX 毒性之间的关系。大多数已发表的报告没有发现 MTHFR 多态性与儿童 ALL 毒性之间的关联。当报告关联时，结果往往相互矛盾。荟萃分析证实了缺乏关联。总之，MTHFR、C677T 和 A1298C 多态性似乎不是儿童 ALL 中与 MTX 相关毒性的良好标志物。
