title: FPGS rs1544105 polymorphism is associated with treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia.
abstract: 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.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiao
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Li
authors.forename: Zhen-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Wu
authors.forename: Hu-Yong
authors.initials: HY
authors.lastname: Zheng
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Zhao
authors.forename: Zhi-Xia
authors.initials: ZX
authors.lastname: Yue
authors.affiliation: Hematology Oncology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, 100045 Beijing, China. ericlzg70@hotmail.com.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Li