These data indicate that FPGS rs1544105, GGH rs3758149, and MTHFR rs1801133 polymorphisms contribute to the variability of MTX pharmacokinetics, and their genotyping may be useful to reduce toxicities associated with MTX therapy.

MicroRNAs (miRNAs) are a class of short non-coding RNA that can specially bind to the 3'-untranslated region of target mRNAs and regulate gene expression at the posttranscriptional level. This study investigated the effects of a miRNA binding site polymorphism (rs1051296) in solute carrier family 19, member 1 (SLC19A1) on serum methotrexate (MTX) concentrations in Chinese children with acute lymphoblastic leukemia (ALL). Genotyping for SLC19A1 rs1051296 G>T in 131 children with ALL was performed using the Sequenom MassArray system. A total of 131 patients received high-dose MTX treatment, and serum MTX concentrations were measured by a fluorescence polarization immunoassay 24 (MTX C24h) and 42 h (MTX C42h) after administration. The frequency of the rs1051296 T allele observed in this study (46.2 %) was significantly lower than that previously observed in a European population (60.7 %, P = 0.002). There was significant association between rs1051296 G>T and MTX C24h (29.97, 32.34, and 39.01 µmol/L for GG, GT, and TT genotypes, respectively, P = 0.04). The percentage of patients with an MTX concentration above the therapeutic threshold (40 μmol/L) was significantly lower in GG carriers compared with that in GT and TT carriers (8.6 % for GG genotype vs. 26.8 and 40.0 % for CT and TT genotypes, respectively, P = 0.02). Delayed elimination of MTX (C42h > 1 μmol/L) was less frequent in GG carriers than in GT and TT carriers. Rs1051296 G>T was associated with MTX plasma concentration, suggesting that miRNAs might be involved in the post-transcriptional regulation of SLC19A1.

No abstract