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Association of folypolyglutamate synthetase (FPGS) gene polymorphism with blood drug concentration as well as adverse reactions of methotrexate in children with acute leukaemia

The aim of this study was to explore the relationship between Folypolyglutamate synthetase (FPGS) gene polymorphism and the blood drug concentration as well as adverse reaction as of Methotrexate (MTX) in children with Acute Lymphocytic Leukaemia (ALL). Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) combined with DNA direct sequencing method was used to analyse the genotype of FPGS-rs1544105 in 51 children with ALL. The blood drug concentration of MTX in patients was determined by using high performance liquid chromatography (HPLC). In addition, the adverse reactions of MTX were also evaluated. The MTX concentration/dose (C/D) values and the incidence of adverse reactions in patients with different FPGS genotypes were compared. FPGSrs1544105 polymorphism showed three genotypes in Chinese ALL children. The minimum allele frequency of G was 35.3%. Although ALL children with GG genotype had the lowest MTX C/D ratio value, no statistical difference was found among the different genotypes (P>0.05). However, GG genotype indeed reduced the risk of neutropenia in ALL children (P=0.032), especially in male patients. FPGS-rs1544105 gene polymorphism may be associated with the adverse reactions of MTX treatment, thus genotype detection before MTX treatment may be helpful to the individualized medication of MTX for ALL patients.

Author(s): Zhen Huang, Hong-Fei Tong, Jiang-Chao Qian, Ju-Xiang Wang, Yuan Li, Min Chen, Zuo Luan