title: A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression.
abstract: A novel single-nucleotide polymorphism (SNP), 829C-->T in the 3'-untranslated region of the human dihydrofolate reductase (DHFR) gene transcript, was identified in the study population of 37 patients with childhood leukemias/lymphomas and 83 healthy Japanese children. Frequencies of the DHFR 829C/C, 829C/T, and 829T/T genotypes were 83.8, 10.8, and 5.4%, respectively, in the cases and 74.7, 19.3, and 6.0% in the controls, showing no significant difference in genotype frequencies between the cases and controls. When determined by real-time quantitative reverse transcription-PCR analysis, the highest expression of the DHFR transcript was demonstrated in the samples with a DHFR 829T/T polymorphism (P < 0.001). Direct association of the presence of the SNP with methotrexate-related adverse events in each patient was not demonstrated in this limited analysis. These data suggest that the novel DHFR 829 polymorphism is associated with a positive role in gene expression and provide evidence of a functional SNP in the 3' regulatory region of the gene.
authors.affiliation: Department of Pediatrics, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-8641, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: L
authors.initials: L
authors.lastname: Yue
authors.forename: A
authors.initials: A
authors.lastname: Yokoi
authors.forename: R
authors.initials: R
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Uehara
authors.forename: S
authors.initials: S
authors.lastname: Koizumi
authors.forename: Y
authors.initials: Y
authors.lastname: Saikawa
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D018076:DNA, Complementary; D012333:RNA, Messenger; D013762:Tetrahydrofolate Dehydrogenase