MTHFR基因多态性对儿童急性淋巴细胞白血病患者应用甲氨蝶呤耐受性的影响

Effect of MTHFR Gene Polymorphism on Methotrexate Tolerance in Children with Acute Lymphoblastic Leukemia

摘要: 目的：探讨MTHFR A1298C和C677T基因多态性对儿童急性淋巴细胞白血病(acute lymphoblastic leukemia, ALL)患者甲氨蝶呤(MTX)耐受性的影响。方法：选取2020年9月至2021年9月于青岛大学附属医院确诊并接受CCCG-ALL2020方案治疗的42例ALL患者，检测患者的MTHFR基因型，结合临床资料分析基因多态性对ALL治疗中HD-MTX方案耐受性的影响。结果：42例患儿中，MTHFR A1298C：AA型27例(64.28%)，AC型15例(35.71%)，未检测到纯合突变型(CC型)；MTHFR C677T：CC型10例(23.8%)，TT型14例(33.33%)，CT型18例(42.85%)。MTHFR A1298C基因不同基因组的MTX化疗不良反应和药代动力学的发生率比较差异均无统计学意义(均P > 0.05)。MTHFR C677T基因多态性与血红蛋白下降、谷丙转氨酶升高和药代动力学方面具有统计学意义(P < 0.05)，而在其他不良反应方面均无统计学意义(P > 0.05)。结论：MTHFR基因多态性不能被视为MTX的毒性标志物，我们可关注其他基因，如转运基因。

Abstract: Objective: To investigate the effect of MTHFR A1298C and C677T gene polymorphisms on metho-trexate (MTX) tolerance in children with acute lymphoblastic leukemia (ALL). Methods: Forty-two ALL patients diagnosed and treated with CCCG-ALL2020 regimen in Affiliated Hospital of Qingdao University from September 2020 to September 2021 were selected. The MTHFR genotype of the pa-tients was detected, and the effect of gene polymorphism on the tolerance of HD-MTX regimen in ALL treatment was analyzed combined with clinical data. Results: Among the 42 children, 27 cases (64.28%) were MTHFR A1298C: AA type, 15 cases (35.71%) were AC type, and no homozygous mu-tation (CC type) was detected; MTHFR C677T: CC type in 10 cases (23.8%), TT type in 14 cases (33.33%), CT type in 18 cases (42.85%). There was no significant difference in the incidence of ad-verse reactions and pharmacokinetics of MTX chemotherapy among different genomes of MTHFR A1298C gene (all P > 0.05). MTHFR C677T gene polymorphism was significantly associated with hemoglobin decrease, alanine aminotransferase increase and pharmacokinetics (P < 0.05), but not with other adverse reactions (P > 0.05). Conclusion: MTHFR gene polymorphism cannot be regarded as a toxicity marker of MTX. We should pay attention to other genes, such as transport genes.