急性淋巴细胞白血病患儿认知功能障碍与MTHFR基因多态性的相关性

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）基因多态性与血浆同型半胱氨酸（Hcy）、认知功能的关系。方法：选取2015年1月至2019年12月于温州医科大学附属第二医院育英儿童医院儿童血液科治疗的39例ALL患儿，采用聚合酶链反应-限制性内切酶片段长度多态性分析（PCR-RFLP）检测MTHFR基因型，韦氏儿童智力量表第四版（WISC-Ⅳ）进行认知功能评估，同时检测Hcy水平，Pearson相关分析MTHFR基因多态性与Hcy水平、认知功能的相关性。结果：ALL患儿MTHFR基因C677T位点存在3种基因型；各基因型比较，TT基因型Hcy水平高于CT和CC型（P＜0.05）；血清Hcy水平与ALL患儿认知功能呈明显负相关，尤其是操作智商；MTHFR 677 C→T基因突变与ALL认知功能负相关（总智商：r=-0.806，P＜0.001；语言智商：r=-0.735，P＜0.001；操作智商：r=-0.802，P＜0.001）。结论：MTHFR基因C677T位点突变可引起血浆Hcy水平升高，进而对认知功能造成影响，可能是认知功能损害的遗传易感因素。

The correlation between cognitive dysfunction and MTHFR gene polymorphism in children with acute lymphoblastic leukemia

Objective: To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine (Hcy) and cognitive function in children with acute lymphoblastic leukemia (ALL). Methods: 39 children with acute lymphoblastic leukemia who were hospitalized in the Department of Hematology of the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University from January 2015 to December 2019 were selected. Polymerase chain reaction-restriction enzyme fragment and length polymorphism analysis (PCR-RFLP) was used to detect the MTHFR genotype. The Wechsler Children’s Intelligence Scale Fourth Edition (WISC-IV) was used to assess cognitive function. Hcy level was also measured to analyze MTHFR. The correlation of gene polymorphism with Hcy level and cognitive function was analyzed by Pearson correlation. Results: Three genotypes existed in the C677T locus of the MTHFR gene in children with acute lymphoblastic leukemia. Compared with each genotype, Hcy level in the TT genotype was higher than that in the CT and CC types (P<0.05). There was a significant negative correlation between serum Hcy level and cognitive function, especially the operational IQ (PIQ) in children with ALL. MTHFR 677 C→T gene mutation was negatively correlated with ALL cognitive function (FIQ: r=-0.806, VIQ: r=-0.735, PIQ: r=-0.802, P<0.001). Conclusion: The MTHFR C677 T gene mutation, which may be a genetic susceptibility factor for cognitive impairment, can increase plasma Hcy levels and then affect cognitive function.