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目的:研究巯基嘌呤甲基转移酶(TPMT)与三磷酸肌苷焦磷酸酶(ITPA)遗传多态性与6-巯基嘌呤在儿童急性淋巴细胞白血病维持治疗中药物不良反应关系。方法:运用等位基因特异性PCR(ASPCR)和PCR-限制性片段长度多态性(PCR-RFLP)的方法分析巯基嘌呤甲基转移酶(TPMT)与三磷酸肌苷焦磷酸酶(ITPA)基因多态性,用HPLC测定TPMT和ITPA活性;参照SFDA的不良反应分析标准分析6-巯基嘌呤在儿童急性淋巴细胞白血病治疗中的不良反应。结果:TPMT*3C组骨髓抑制几率高于野生基因组。尚未发现TPMT与ITPA的基因多态性与肝脏受损、胃肠道反应联系。结论:临床6-巯基嘌呤治疗前,筛查TPMT基因突变进行剂量调整可避免骨髓抑制发生,TPMT与ITPA遗传多态性与6-巯基嘌呤的关系,尚需结合药物相互作用与其他药物代谢酶的遗传多态性进一步研究。
Objective: To investigate the relationship between the genetic polymorphisms of thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) and the side effects of 6-mercaptopurine in the maintenance of childhood acute lymphoblastic leukemia. Methods: The expressions of thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) were assayed by allele specific PCR (ASPCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) The polymorphisms of TPMT and ITPA were determined by HPLC. The adverse reactions of 6-mercaptopurine in the treatment of childhood acute lymphoblastic leukemia were analyzed according to the standard of adverse reaction analysis of SFDA. Results: The bone marrow suppression rate in TPMT * 3C group was higher than that in wild type. The genetic polymorphisms of TPMT and ITPA have not been found to be associated with impaired liver and gastrointestinal reactions. Conclusion: Before clinical treatment of 6-mercaptopurine, the screening of TPMT gene mutation dose can avoid the occurrence of myelosuppression. The relationship between TPMT and ITPA genetic polymorphism and 6-mercaptopurine still need to be combined with drug-drug interactions and other drug-metabolizing enzymes The genetic polymorphism is further studied.