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目的考察多药耐药基因1(MDR1)C3435T多态性与急性淋巴细胞白血病(ALL)患儿甲氨蝶呤(MTX)血清浓度及化疗毒性的相关性。方法收集100例ALL患儿外周血,提取基因组DNA;用PCR-RFLP法,检测MDR1 C3435T基因型;用荧光偏振免疫法(FPIA),测定MTX血清浓度,同时观察化疗的疗效和毒性。结果 CC、CT和TT基因型的分布频率分别为33%,53%,14%;C和T等位基因的分布频率分别为59.5%和40.5%。肝功能异常ALL患儿,其24,42h MTX剂量校正的血清浓度(C/D比值)高于肝功能正常者;携带野生基因型(CC)ALL患儿的24,42 h MTX C/D比值高于突变基因型(CT+TT)携带者;携带野生基因型ALL患儿的未缓解、化疗毒性和排泄延迟发生率,高于突变基因型携带者。由于个体间的变异大,上述差异均无统计学意义(P>0.05)。结论多种因素影响MTX的药代与药效,MDR1 C3435T多态性与ALL患儿的MTX血清浓度和化疗毒性无显著相关关系。
Objective To investigate the relationship between multidrug resistance gene 1 (MDR1) C3435T polymorphism and methotrexate (MTX) serum concentration and chemotherapy toxicity in children with acute lymphoblastic leukemia (ALL). Methods Genomic DNA was extracted from 100 children with ALL. The genotypes of MDR1 C3435T were detected by PCR-RFLP. The serum concentration of MTX was measured by fluorescence polarization immunoassay (FPIA). The curative effect and toxicity of chemotherapy were also observed. Results The frequencies of CC, CT and TT genotypes were 33%, 53% and 14%, respectively. The frequencies of C and T alleles were 59.5% and 40.5%, respectively. The serum C / D ratio (C / D ratio) of 24,42 h MTX dose-corrected children with ALL with abnormal liver function was higher than those with normal liver function. The MTX C / D ratios of 24 and 42 h in children with wild type CC Higher than the mutant genotype (CT + TT) carriers; children with wild genotypes untreated, chemotherapy toxicity and excretion delay was higher than the mutant genotype carriers. Due to the large variation among individuals, the above differences were not statistically significant (P> 0.05). Conclusion There are many factors that affect the pharmacokinetics and efficacy of MTX. There is no significant correlation between MDR1 C3435T polymorphism and MTX serum concentration and chemotherapy toxicity in children with ALL.