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Genotype and allele frequencies of TYMS rs2790 A > G polymorphism in a Chinese paediatric population with acute lymphoblastic leukaemia
Author(s) -
Wang S.M.,
Zeng W.X.,
Wu W.S.,
Sun L.L.,
Yan D.
Publication year - 2018
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/jcpt.12678
Subject(s) - genotyping , genotype , allele , thymidylate synthase , minor allele frequency , medicine , pharmacogenetics , methotrexate , population , allele frequency , biology , gastroenterology , immunology , genetics , chemotherapy , gene , fluorouracil , environmental health
Summary What is known and objective Thymidylate synthase ( TYMS ) is an important target for methotrexate ( MTX ). Genetic variations in the TYMS gene contribute to the differences in treatment responses to MTX . The aim of this study was to investigate the distribution of a micro RNA (mi RNA ) binding site polymorphism (rs2790 A > G) in the 3′‐untranslated region (3′‐ UTR ) of TYMS and its association with MTX concentration and haematological toxicity in Chinese paediatric patients with acute lymphoblastic leukaemia ( ALL ). Methods The Sequenom Mass ARRAY system was used for TYMS rs2790 A > G genotyping in 118 children with ALL . Serum MTX concentrations were measured by a fluorescence polarization immunoassay. Clinical data were extracted from the electronic medical records. Results and discussion The minor allele frequency noted in this study (39.8%) was significantly higher than those in the CEU (Utah residents with northern and western Europe ancestry; 16.2%) and YRI (Yoruba in Ibadan, Nigeria; 25.0%) samples reported in the 1000 Genomes Project ( P < .01). The frequency of MTX level >40 μmol/L at 24 hours in patients with the AA genotype (36.6%) was significantly higher than that in GG genotype carriers (5.9%, P < .05). However, the incidence rates of haematological toxicity were similar in the three genotype groups. Whereas there was evidence of higher blood levels in the A homozygotes, the evidence for this translating to higher toxicity was lacking. A larger study would be required to answer this. What is new and conclusion The results of this study confirmed the significant ethnic differences in the distributions of the TYMS rs2790 A > G polymorphism. Whereas there was evidence of differences in MTX blood levels according to genotype, our study was not powered to show whether this would lead to more haematological toxicity.