摘要
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 association between multi-drug resistance 1（MDR1） C3435T polymorphism with serum concentrations and toxicities of methotrexate（MTX） in children with acute lymphoblastic leukemia（ALL）.Methods A total of 100 peripheral blood samples were obtained from children with acute lymphoblastic leukemia to extract genome DNA.PCR-RFLP was used to detect the genotypes of MDR1 C3435T polymorphism.FPIA was employed to determine the serum concentrations of MTX in 24 h and 42 h.The treatment responses of MTX were 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 dose-adjusted serum concentration（C/D ratio） of MTX in ALL children with abnormal liver function in 24 h and 42 h were higher than those with normal liver function.Compared with wild genotype（CC） carriers,mutant genotype（CT/TT） carriers had lower C/D ratios of MTX in 24 h and 42 h.The incidences of non-remission,toxicities and delayed elimination in wild genotype carriers were higher than those in mutant genotype carriers.Due to the high inter-individual variation,the differences above were not significant（P0.05）.Conclusion Multiple factors affected the pharmacokinetics and pharmacodynamics of MTX.There were no significant assiciations between MDR1 C3435T polymorphism with serum concentration and toxicities of MTX in ALL children.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2012年第1期20-23,共4页
The Chinese Journal of Clinical Pharmacology
