中文摘要：

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。

英文摘要：

OBJECTIVE To study the relationship between genetic polymorphism of thiopurine methyltransferase （TPMT） and inosine triphosphate pyrophosphatase （ITPA） with adverse drug reactions in 6-mercaptopurine in maintenance treatment of childhood acute lymphoblastic leukemia. METHODS Method of the allele specific PCR （ASPCR） and PCR-restriction fragment length polymorphism （PCR-RFLP） analysis the polymorphism of thiopurine methyltransferase （TPMT） and inosine triphosphate pyrophosphatase （ITPA）, HPLC was used for the determination of TPMT and ITPA activity, reference to the adverse reactions of SFDA standards was taken as the reference for evaluation of the adverse reactions of 6-mercaptopurine treatment in children with acute lymphoblastic leukemia. RESULTS Risk of bone marrow suppression of TPMT ＊ 3C is higher than wild genome. It was not found that the gene TPMT and ITPA polymorphisms linked with liver damage and gastrointestinal reactions. CONCLUSION Dosage adjustment in TPMT gene mutation can avoid the occurrence of bone marrow suppression. The relationship between TPMT and ITPA polymorphism and 6-mercaptopurine still need to integrate drug interactions with other drug metabolism enzymes in further study of genetic polymorphism.