叶酰多聚谷氨酸合成酶基因多态性对急性白血病患儿大剂量甲氨蝶呤治疗的影响  

Influence of Folylpolyglutamate Synthetase Genetic Polymorphism on Treatment of Methotrexate in Acute Lymphocytic Leukemia Patients

作　　者：黄珍[1] 王菊香[1] 钱江潮[1] 李原[1] 

机构地区：[1]温州医科大学附属第二医院育英儿童医院血液科,浙江温州325003

出　　处：《中国药学杂志》2015年第17期1536-1540,共5页Chinese Pharmaceutical Journal

基　　金：温州市科技计划资助项目(Y20140255)

摘　　要：目的探讨叶酰多聚谷氨酸合成酶(FPGS)基因多态性与急性白血病患儿甲氨蝶呤(MTX)动态血药浓度及预后的相关性。方法对57例急性淋巴细胞白血病患儿和31例对照组儿童,应用聚合酶链-限制性片段长度多态性法分析FPGS-rs1544105位点基因型;高效液相色谱法24、44 h测定甲氨蝶呤血药浓度;比较不同基因型患儿甲氨蝶呤浓度的差异;并随访复发及死亡等情况进行生存分析。结果急性淋巴细胞白血病患儿与健康对照人群的基因型与等位基因分布频率相近,差异无统计学意义;携带AA型患儿24 h甲氨蝶呤浓度明显高于携带GG型和GA型者(P<0.05);各基因型44 h的甲氨蝶呤浓度未见差异;Kaplan-Meier生存分析结果显示,FPGS-rs1544105 AA基因型中位生存时间高于其他基因型,总体生存率存在统计学差异(P<0.05)。结论 FPGS rs1544105基因多态性可能可以做为甲氨蝶呤药物治疗疗效预测的有效生物学手段。OBJECTIVE To explore the correlation between genetic polymorphism of folylpolyglutamate synthetase （ FPGS）, plasma concentrations of methotrexate （MTX） and prognosis in patients with acute leukemia. METHODS PCR-restriction fragment length polymophism（PCR-RFLP） was used to detect the genetic polymorphisms of FPGS rs1544105 in ALL patients（ n = 57 ） and the control individual（ n = 31 ）. The plasma concentrations of MTX were measured by high performance liquid chromatography （HPLC） at the times of 24 and 44 h. The association between targeted polymorphisms and MTX concentration-to-dose （C/D） ratios was assessed. According to the result of follow up, survival curve was analyzed. RESULTS Similar frequencies of genotypes and alleles were found at FPGS rs1544105 in healthy subjects and ALL patients. In the genotype of AA, MTX C/D ratio at the time of 24 h was higher than the others （ P 〈 0. 05 ）. While there was not a significant difference at 44 h （P 〉 0. 05 ）. Kaplan-Meier survival analysis showed that median survival time of AA genotype was longer than others. Overall survival （OS） rate was statistically different （P 〈 0. 05 ）. CONCLUSION Folylpolyglutamate synthetase （FPGS） genetic polymorphism may be a useful method to predict the effectiveness of methotrexate.

关 键 词：叶酰多聚谷氨酸盐合成酶 基因多态性 甲氨蝶呤 白血病 

分 类 号：R969.4[医药卫生—药理学]