title: Identification of missense mutations in the hepatocyte nuclear factor-3beta gene in Japanese subjects with late-onset Type II diabetes mellitus.
abstract: OBJECTIVE
  Hepatocyte nuclear factor (HNF)-3beta, a transcription factor expressed in pancreatic beta cells, is an upstream regulator of HNF-1alpha/MODY3, HNF-4alpha/MODY1 and IPF1/MODY5 genes. Our previous screening of MODY subjects showed that mutations in the HNF-3beta gene are not a common cause of this form of diabetes in the Japanese. We tested the hypothesis that mutations in the HNF-3beta gene cause late-onset Type II (non-insulin-dependent) diabetes mellitus in this population.
  
  
  METHODS
  Genotyping of the polymorphic TCC repeat in the HNF-3beta gene was done in 112 Japanese subjects with Type II diabetes (age at diagnosis > 35 and family history of Type II diabetes among their second-degree relatives) and 96 Japanese control subjects. Furthermore, we screened 57 Type II diabetic patients for mutations of the HNF-3beta gene. Transactivation activity of variant HNF-3beta was investigated by transfection assay.
  
  
  RESULTS
  The distribution of alleles of the TCC repeat was similar between diabetic and control groups. Mutation screening identified two missense mutations, A86T and G114E. Neither mutation was observed in 225 control subjects. The transactivation activity of G114E-HNF-3beta was similar to that of wild typeHNF-3beta. In contrast, the activity of A86T-HNF-3beta was statistically significantly reduced to 83-86 % of that of wild type.
  
  
  CONCLUSIONS
  The A86T mutation in the HNF-3beta gene might be involved in the development of late-onset Type II diabetes in a small group of Japanese people.
authors.affiliation: The Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Japan.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: K
authors.initials: K
authors.lastname: Yamagata
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Tomura
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: I
authors.initials: I
authors.lastname: Yoshiuchi
authors.forename: S
authors.initials: S
authors.lastname: Sumi
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.forename: J
authors.initials: J
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People; D003062:Codon; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D017930:Genes, Reporter; D005838:Genotype; D006367:HeLa Cells; D051542:Hepatocyte Nuclear Factor 3-beta; D006801:Humans; D007564:Japan; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D018911:Trinucleotide Repeats
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta