转运蛋白基因多态性对儿童急性淋巴细胞白血病大剂量甲氨蝶呤治疗的影响

Influence of transport protein gene polymorphisms on the effects and toxicity of high-dose methotrexate in childhood acute lymphoblastic leukemia

目的研究多药耐药基因1(MDR1)和还原型叶酸载体基因(SLC19A1)多态性对儿童急性淋巴细胞白血病(ALL)大剂量甲氨喋呤(MTX)治疗疗效及不良反应的影响。方法应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOFMS)技术,对108例ALL患者MDR1 exon26C>T、MDR1 exon21G>T/A和SLC19A1 80G>A基因多态性进行分析;并分析基因型和生存率、不良反应等的关系。结果 MDR1 exon26C>T、MDR1 exon21G>T/A和SLC19A180G>A各基因型的36个月生存率差异无统计学意义;MDR1 exon26C>T和MDR1 exon21G>T/A突变型的24 h MTX血浆浓度高于野生型,且突变型具有更高的肝功能损伤发生率,差异均有统计学意义(P<0.05)。结论 MDR1 exon26C>T和MDR1 exon21G>T/A基因突变对大剂量MTX治疗血浆浓度及肝功能损伤有明显影响。

Objectives To investigate the influence of polymorphisms of SLC19A1 80G＆gt;A,MDR1 exon26C＆gt;T and MDR1 exon21G＆gt;T/A on curative effect and adverse reaction of high-dose methotrexate in patients with acute lymphoblastic leukemia.Methods MALDI-TOF-MS technique was used to detect the polymorphisms of SLC19A1 80G＆gt;A,MDR1 exon 26C＆gt;T and MDR1 exon21G＆gt;T/A in 108 patients with acute lymphoblastic leukemia（ALL）.The relationship of genetic polymorphism,survival rate and toxicity was analyzed.Results The 36-month event-free survival was not related to any polymorphisms of MDR1 and SLC19A1.Patients with mutant types of MDR1 exon26C＆gt;T and MDR1 exon21G＆gt;T/A showed a much higher MTX plasma levels at 24 hours and higher incidence of hepatic injury（P＆lt;0.05）.Conclusions The genetic polymorphism of MDR1 exon26＆gt;T,MDR1 exon21G＆gt;T/A has a large influence on hepatic toxicity and plasma concentrations of MTX.