Background: Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. FPGS tag SNP rs1544105C > T is located in the gene promoter. The aim of the present study was to investigate the impact of rs1544105 polymorphism on the treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods: This study enrolled 164 children with BCP-ALL. We genotyped the FPGS SNP rs1544105, and analyzed the associations between its genotypes and treatment outcome. We also examined FPGS mRNA levels by real-time PCR in 64 of the 164 children, and investigated the function of this polymorphism on gene expression. Results: We found significantly poor relapse-free survival (RFS) (p = 0.010) and poor event-free survival (EFS) (p = 0.046) in carriers of CC genotype. Multivariable Cox regression analyses adjusted for possible confounding variables showed that, relative to the CT + TT genotypes, the CC genotype was an independent prognostic factor for poor RFS (hazard ratio [HR], 4.992.; 95% CI, 1.550-16.078; p = 0.007). No association was found between any toxicity and rs1544105 polymorphism. Quantitative PCR results showed that individuals with the T allele had lower levels of FPGS transcripts. Conclusions: Our study indicates that FPGS rs1544105C > T polymorphism might influence FPGS expression and affect treatment outcome in BCP-ALL patients.
基金：
project of National Key Technologies Research & Development Program of the 11th 5-Year Plan [2007BAI04B03]; National Science & Technology Major Project of the 12th 5-Year Plan [2011ZX09302-007-01]; Capital Medical University Basic & Clinical Research Cooperation Foundation [13JL72]
通讯机构：[1]Capital Med Univ, Hematol Oncol Ctr, Beijing Key Lab Pediat Hematol Oncol, Natl Key Discipline Pediat,Beijing Childrens Hosp, Beijing 100045, Peoples R China;[2]Capital Med Univ, Hematol Oncol Ctr, Beijing Key Lab Pediat Hematol Oncol, Natl Key Discipline Pediat,Beijing Childrens Hosp, 56 Nanlishi Rd, Beijing 100045, Peoples R China
推荐引用方式(GB/T 7714)：
Liu Shu-Guang,Gao Chao,Zhang Rui-Dong,et al.FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia[J].CANCER CELL INTERNATIONAL.2013,13(1):-.doi:10.1186/1475-2867-13-107.
APA：
Liu, Shu-Guang,Gao, Chao,Zhang, Rui-Dong,Jiao, Ying,Cui, Lei...&Li, Zhi-Gang.(2013).FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia.CANCER CELL INTERNATIONAL,13,(1)
MLA：
Liu, Shu-Guang,et al."FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia".CANCER CELL INTERNATIONAL 13..1(2013):-
