title: Genetic variation in the hepatocyte nuclear factor (HNF)-3alpha gene does not contribute to maturity-onset diabetes of the young in Japanese.
abstract: Heterozygous mutations in the genes encoding transcription factors in the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of diabetes mellitus. However, these genes are responsible for only approximately 20% of the cases of MODY in Japanese patients. Searching for a novel MODY gene in this population, we investigated a candidate for encoding the forkhead transcription factor HNF-3alpha, which also belongs to the HNF-transcription cascade. The human HNF-3alpha gene, which was assigned to the segment near microsatellites D14S75 and AFM200ZH4 on chromosome 14 by radiation hybrid mapping, spans approximately 5 kb and consists of two exons. Ninety-five Japanese subjects with MODY/early-onset non-ketotic diabetes were screened for mutations in this gene. Direct sequencing of the exons and flanking regions identified one missense mutation (Ala-83-Thr) in exon 2 and three nucleotide alterations in the non-coding regions. However, their frequencies were not significantly different between MODY and control subjects, indicating that mutations in the HNF-3alpha gene are not a major cause of MODY in Japanese patients.
authors.affiliation: Department of Cell Biology, Institute for Molecular and Cellular Regulation, Maebashi, Gunma, Japan.
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.forename: H
authors.initials: H
authors.lastname: Nishigori
authors.forename: T
authors.initials: T
authors.lastname: Nishigori
authors.forename: H
authors.initials: H
authors.lastname: Tomura
authors.forename: J
authors.initials: J
authors.lastname: Fujita
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
authors.forename: J
authors.initials: J
authors.lastname: Takeda
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D014644:Genetic Variation; D051541:Hepatocyte Nuclear Factor 3-alpha; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors