亚甲基四氢叶酸还原酶基因1298及677位点多态性与急性淋巴细胞白血病患儿甲氨蝶呤化疗毒副作用的相关性

Correlation between Methylene Tetrahydrofolate Reductase Gene Polymorphisms at 1298 and 677 and Toxicity of Methotrexate Chemotherapy in Children with Acute Lymphoblastic Leukemia

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因1298、677位点多态性与急性淋巴细胞白血病(ALL)患儿甲氨蝶呤(MTX)化疗毒副作用的相关性。方法:分析2014年7月至2017年10月在我院就诊的98例ALL患儿应用MTX化疗和恢复期的临床资料,比较677位点和1298位点基因突变后的不同基因型个体在高剂量MTX化疗后的代谢水平以及毒副作用。结果:MTHFR C677T突变基因个体比野生型的基因个体更易发生胃肠道反应,A1298C突变基因个体比野生型的基因个体更易发生口腔黏膜损害; MTHFR基因的A1298C突变基因个体骨髓抑制的风险低于野生型的基因个体; A1298C突变基因携带个体延长了MTX代谢时间。结论:本研究为ALL患儿在基因诊断和筛查时提供个体样本筛查指标,有利于订制更为有效的治疗方案,从而在化疗周期中降低患儿黏膜毒副作用。

Objective: To investigate the correlation between methylene tetrahydrofolate reductase(MTHFR) gene polymorphisms at1298 and 677 and the toxicity of methotrexate( MTX) chemotherapy in children with acute lymphoblastic leukemia( ALL). Methods:The clinical data of 98 children with ALL undergoing MTX chemotherapy admitted into our hospital from Jul. 2014 to Oct. 2017 were analyzed. Different genotype individuals after mutation of 677 and 1298 genes,metabolic levels and toxicity after high-dose MTX chemotherapy were compared. Results: Individuals with MTHFR C677 T mutation were more likely to have gastrointestinal reactions than those with wild-type mutation. Individuals with A1298 C mutation were more likely to suffer oral mucosal damage than those with wildtype mutation. The risk of bone marrow suppression was lower in individuals with MTHFR A1298 C mutation than in individuals with wild-type. The A1298 C mutant gene carried an individual that prolong the metabolic time of MTX. Conclusion: This study provides individual sample screening indicators for children with ALL in genetic diagnosis and screening,which is conducive to the preparation of more effective treatment options to reduce mucosal toxicity in children during the chemotherapy cycle.