急性淋巴细胞白血病患儿MTHFR C677T基因多态性与大剂量甲氨蝶呤治疗后肝功能异常的相关性

目的：探讨急性淋巴细胞白血病（ALL）患儿亚甲基四氢叶酸还原酶（MTHFR）C677T基因多态性与大剂量甲氨蝶呤（HD-MTX）治疗后肝功能异常的相关性。方法：收集2017年10月至2020年3月温州医科大学附属第二医院育英儿童医院66例ALL患儿HD-MTX治疗的临床资料，检测MTHFR C677T的基因多态性，根据基因型将患儿分为野生型（CC）和突变型（CT+TT），比较2组患儿经HD-MTX治疗后不良反应的发生率、肝功能指标PA、ALT、AST、AST/ALT、TP、ALB、LDH、GGT、TBIL、CHE以及48 h、72 h血药浓度的差异。结果：MTHFR C677T突变型与野生型相比肝功能异常的发生率更高（P＜0.05），其中血清AST、ALT、CHE含量异常的患儿比例显著升高（P＜0.05），其他肝功能指标差异无统计学意义（P＞0.05）。进一步分析不同基因型患儿HD-MTX血药浓度的差异，结果显示与野生型相比，突变型48 h、72 h血药浓度均升高（P＜0.05）。结论：MTHFR C677T突变型患儿HD-MTX治疗后，血清AST、ALT、CHE含量异常的患儿比例较高，检测MTHFR C677T基因型对预测HD-MTX治疗后肝功能异常有一定的临床应用价值。

The correlation between MTHFR C677T gene polymorphism and abnormal liver function in pediatric acute lymphoblastic leukaemia after treatment with high-dose methotrexate

Objective: To investigate the correlation between MTHFR C677T gene polymorphism and abnormal liver function in pediatric acute lymphoblastic leukemia (ALL) after treatment with high-dose methotrexate (HD-MTX). Methods: The clinical data of 66 children with ALL treated with HD-MTX in the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University from October 2017 to March 2020 were analyzed retrospectively. According to the genotype of MTHFR C677T, the children were divided into wild group (CC) and mutant group (CT+TT) to compare differences in incidence of toxicity, liver function indexes PA, ALT, AST, AST/ALT, TP, ALB, LDH, GGT, TBIL, CHE and blood drug concentrations at 48 h and 72 h after HD-MTX treatment. Results: Compared with the wild group, MTHFR C677T mutation group had a higher incidence of abnormal liver function (P<0.05), in which the proportion of children with abnormal levels of AST, ALT and CHE increased significantly (P<0.05), but there was no significant difference in other liver function indexes (P>0.05). Further analysis of the difference in HD-MTX concentrations between different genotypes showed that the mutant type, compared with the wild type, had higher blood drug concentrations at 48 h and 72 h (P<0.05). Conclusion: The proportion with abnormal levels of serum AST, ALT and CHE is higher for children with MTHFR C677T mutation type after treatment with HD-MTX, and detection of MTHFR C677T genotype has clinical application value in predicting abnormal liver function after HD-MTX treatment.