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目的:研究谷胱甘肽硫转移酶(GSTs)家族中GSTT1、GSTM1基因多态性与儿童急性淋巴细胞白血病(ALL)早期治疗反应和化疗不良反应的关系。方法:筛选ALL患者98例,采用多重PCR技术分析GSTT1、GSTM1基因型,比较不同基因型患者早期治疗反应和发生化疗毒副作用的差异。结果:GSTT1基因缺失型患者早期治疗反应较GSTT1基因非缺失型患者好(OR=3.35,95%CI:1.05～10.73,P=0.041),GSTT1和GSTM1基因双非缺失型患者发生早期治疗反应差的风险明显高于GSTT1和GSTM1任一基因缺失型及双缺失型(OR=5.73,95%CI:1.73～18.95,P=0.004)。GSTM1基因缺失型患者发生口腔黏膜炎、肝功能异常及感染的风险高于GSTM1基因非缺失型患者(P<0.05),GSTT1和GSTM1基因双缺失型患者发生肝功能异常及感染的风险明显高于两基因非双缺失型患者(P<0.05)。结论:GSTT1和GSTM1基因型与ALL患者早期治疗反应及化疗不良反应发生率相关,GSTT1和GSTM1基因型有助于指导ALL患者个体化治疗方案的制定。
Objective: To investigate the relationship between GSTT1 and GSTM1 gene polymorphism and early treatment response and adverse reaction of chemotherapy in children with acute lymphoblastic leukemia (ALL) in the glutathione S-transferase (GSTs) family. Methods: A total of 98 patients with ALL were screened. The genotypes of GSTT1 and GSTM1 were analyzed by multiplex PCR. The differences between the early treatment response and the chemotherapy side effects in different genotypes were compared. Results: The early treatment response of GSTT1 gene deletion patients was better than that of non GSTT1 gene deletion patients (OR = 3.35, 95% CI: 1.05-10.73, P = 0.041). The patients with GSTT1 and GSTM1 gene double non-deletion had poor response to early treatment (OR = 5.73, 95% CI: 1.73 ~ 18.95, P = 0.004), which was significantly higher than that of GSTT1 and GSTM1. The risk of oral mucositis, abnormal liver function and infection in patients with GSTM1 deletion was higher than that in non-deletion patients with GSTM1 gene (P <0.05). The risk of liver dysfunction and infection in patients with GSTT1 and GSTM1 double deletion were significantly higher than those without GSTM1 Two genes in patients with non-double deletion (P <0.05). Conclusion: The genotypes of GSTT1 and GSTM1 are associated with the early response to chemotherapy and the incidence of adverse reactions in patients with ALL. The genotypes of GSTT1 and GSTM1 are helpful to guide the development of individualized treatment for ALL patients.