亚甲基四氢叶酸还原酶基因多态性与急性淋巴细胞白血病患者甲氨蝶呤化疗毒副反应的研究

本研究旨在观察mthfr基因多态性分布对急性淋巴细胞白血病患者使用大剂量MTX化疗后毒副反应的影响。收集44例ALL患者外周血，提取基因组DNA，用PCR—RFLP技术检测mthfr基因型；观察经大剂量甲氨蝶呤化疗后所有患者的药后毒副作用。结果表明：mthfrC677T和A1298C各基因型间毒副反应差异显著，携带T突变基因患者发生毒副反应是携带CC基因型的3．75倍；携带AC＋CC基因型发生毒副反应是AA基因型携带者的0．12倍。mthfr677TT基因型联合1298AA基因型与677CC基因型同时携带1298C等位基因变异患者在毒副反应上差异显著，前者发生毒副作用的可能性是后者的16．5倍。结论：mthfr基因多态性分布与ALL患者HDMTX化疗后的毒副反应有关。

Association between Mthfr Gene Polymorphisms and Toxicity of HDMTX Chemotherapy in Acute Lymphocytic Leukemia

This study was aimed to investigate the association between mthfr gene polymorphisms and toxicity of HDMTX in acute lymphocytic leukemia patients. A total of 44 patients were selected, and DNA was extracted from their peripheral blood. PCR-RFLP was used to determine the genotypes of mthfr. The toxicity response of patients received HDMTX chemotherapy was observed. The results showed that the toxicity of HDMTX to carriers of the variant allele at codon 677 (CT or TT) increased, as compared with individuals with the common CC genotype (OR = 3.75, 95% CI 1 - 14, p = 0.04). In contrast, the toxicity of HDMTX to ALL patients with the variant allele at codon 1298 (AC or CC) decreased as compared with the common AA genotype carriers (OR = 0.12, 95% CI: 0.026 - 0.564, p = 0.007). As compared with carriers of the variant allele at coden 1298 (AC or CC), the toxicity of HDMTX to patients with TT genotype at 677 and AA genotype at 1298 increased (OR = 16.5, 95% CI: 0.026 - 0.564). It is concluded that mthfr gene polymorphisms associate with the toxicity of HDMTX chemotherapy in acute lymphocytic leukemia.