Influence of folylpolyglutamate synthetase genetic polymorphism on treatment of methotrexate in acute lymphocytic leukemia patients
- Author:
Zhen HUANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Folylpolyglutamate synthetase; Genetic polymorphism; Leukemia; Methotrexate
- From: Chinese Pharmaceutical Journal 2015;50(17):1536-1540
- CountryChina
- Language:Chinese
- 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.