title: Beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the hepatocyte nuclear factor-3beta gene (HNF3B) in Japanese patients with maturity-onset diabetes of the young.
abstract: Mutations in the transcription factors hepatocyte nuclear factor (HNF)-4alpha and -1alpha, insulin promoter factor-1, and HNF-1beta are the causes of four forms of maturity-onset diabetes of the young (MODY1 and 3-5, respectively). The winged-helix transcription factor HNF-3beta has been implicated in the regulation of expression of each of these MODY genes, suggesting that mutations in the HNF-3beta gene (HNF3B) may also cause MODY. We have tested this hypothesis by screening a panel of 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in HNF3B. This analysis revealed four frequent polymorphisms that were not associated with MODY, including one in the promoter region (-213A/G), two silent mutations in the codons for Ala 97 (291C/T) and Gly 279 (837A/G), and one in the 3'-untranslated region (1424C/T). Two rare substitutions in the 5'-untranslated region, -156C/T and -67A/C, were found in a heterozygous state in two subjects, and two subjects were heterozygous for putative missense mutations, S109N (326G > A) and A328V (983C>T). The two missense mutations were not found in 106 normal chromosomes from nondiabetic subjects. It was not possible to test for co-segregation of these mutations with diabetes and thus, it is unclear whether or not these mutations can cause MODY. The results of our study suggest that mutations in HNF3B are not a common cause of MODY in Japanese subjects.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry, University of Chicago, Illinois 60637, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hinokio
authors.forename: Y
authors.initials: Y
authors.lastname: Horikawa
authors.forename: H
authors.initials: H
authors.lastname: Furuta
authors.forename: N J
authors.initials: NJ
authors.lastname: Cox
authors.forename: N
authors.initials: N
authors.lastname: Iwasaki
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: M
authors.initials: M
authors.lastname: Ogata
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D051542:Hepatocyte Nuclear Factor 3-beta; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D007564:Japan; D008297:Male; D009154:Mutation / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta