Huang Zhen, Tong Hong-Fei, Li Yuan, Qian Jiang-Chao, Wang Ju-Xiang, Wang Zhe, Ruan Ji-Chen
Department of Hematology, Yuying Children's Hospital, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).
Med Sci Monit. 2016 Dec 17;22:4967-4973. doi: 10.12659/msm.899021.
BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. MATERIAL AND METHODS 57 ALL patients and 31 age and sex-matched children (control) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of the genotype of FPGS rs1544105 and high-performance liquid chromatography for measurement of MTX plasma concentration after 24-h and 44-h treatment. Overall survival was analyzed by Kaplan-Meier method. RESULTS No differences were observed between patients and controls regarding the distribution frequency of genotype and alleles of rs1544105. Patients carrying AA genotype had a significantly higher plasma concentration of MTX after 24 h than those carrying GG or GA (P<0.05) and no differences were found after 44 h. Kaplan-Meier survival analysis showed a longer median survival time in patients with AA than other genotypes with significant difference in overall survival. CONCLUSIONS Polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment outcome of MTX.
背景 本研究旨在探讨小儿急性淋巴细胞白血病（ALL）患者中叶酸多聚谷氨酸合成酶（FPGS）基因多态性与甲氨蝶呤（MTX）动态血药浓度及预后的关系。材料与方法 本研究纳入57例ALL患者及31例年龄和性别匹配的儿童（对照组）。采用聚合酶链反应-限制性片段长度多态性方法分析FPGS rs1544105基因型，采用高效液相色谱法测定治疗24小时和44小时后MTX血药浓度。采用Kaplan-Meier法分析总生存期。结果 在rs1544105基因型和等位基因的分布频率方面，患者与对照组之间未观察到差异。携带AA基因型的患者在24小时后的MTX血药浓度显著高于携带GG或GA基因型的患者（P<0.05），而在44小时后未发现差异。Kaplan-Meier生存分析显示，AA基因型患者的中位生存期长于其他基因型，总生存期有显著差异。结论 FPGS rs1544105基因多态性可能作为预测MTX治疗效果的有效方法。
