MTHFR基因多态性与ALL患儿MTX血药浓度及严重毒副反应的相关性研究

目的：在儿童急性淋巴细胞白血病（ALL）患者中，探讨亚甲基四氢叶酸还原酶（MTHFR C677T和A1298C）基因多态性与甲氨蝶呤（MTX）化疗后44 h血药浓度和严重毒副反应间的相关性。方法：收集77例ALL患儿临床资料，监测MTX输注后44 h的血药浓度并进行MTHFR基因分型；分析MTHFR C677T基因型和A1298C基因型与MTX 44 h血药浓度及严重毒副反应间的相关性。结果：MTHFR C677T、A1298C各基因型与MTX 44 h血药浓度间均无统计学差异（P>0.05）。未发现MTHFR C677T基因多态性与MTX化疗后严重毒副反应间存在相关性（P>0.05）。MTHFR A1298C杂合突变型（AC）相比野生型（AA），发生血红蛋白减少的风险增加（P=0.002），未发现其他严重毒副反应与MTHFR A1298C基因多态性间存在相关性（P>0.05）。结论：MTHFR A1298C基因多态性可能与ALL患儿MTX化疗后血红蛋白减少有一定相关性。

Correlation of MTHFR Gene Polymorphism with MTX Plasma Concentration and Severe Toxicity in Children with ALL

Objective: To investigate the correlation among C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene, methotrexate (MTX) plasma concentrations at 44 h and severe adverse reactions after MTX chemotherapy in children with acute lymphoblastic leukemia (ALL). Methods: Clinical data of 77 children with ALL were collected. The plasma concentrations of MTX at 44 h after infusion were monitored and the MTHFR genotyping was performed. The association of polymorphisms of MTHFR C677T and A1298C genotypes with MTX plasma concentrations at 44 h and severe adverse reactions was analyzed. Results: There were no statistical differences between MTHFR C677T, A1298C genotypes and MTX plasma concentrations at 44 h(P>0.05). No correlation was found between MTHFR C677T gene polymorphism and severe adverse reactions after MTX chemotherapy (P>0.05). MTHFR A1298C heterozygous mutant (AC) had an increased risk of hemoglobin reduction compared to wild type (AA) (P=0.002). But no significant difference between MTHFR A1298C polymorphism and other severe toxicities was observed (P>0.05). Conclusion: MTHFR A1298C gene polymorphism may be associated with hemoglobin reduction after MTX chemotherapy in children with ALL.