title: Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Wang
authors.forename: Lu-lu
authors.initials: LL
authors.lastname: Sun
authors.forename: Wei-xin
authors.initials: WX
authors.lastname: Zeng
authors.forename: Wan-shui
authors.initials: WS
authors.lastname: Wu
authors.forename: Guo-liang
authors.initials: GL
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000097:blood* / Q000627:therapeutic use; D035683:MicroRNAs / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D058978:Reduced Folate Carrier Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D035683:MicroRNAs; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D008727:Methotrexate