Abstract��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.
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HUANG Zhen, WANG Ju-xiang, QIAN Jiang-chao, LI Yuan. Influence of Folylpolyglutamate Synthetase Genetic Polymorphism on Treatment of Methotrexate in Acute Lymphocytic Leukemia Patients. Chinese Pharmaceutical Journal, 2015, 50(17): 1536-1540.
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