title: Genetic variation in the hepatocyte nuclear factor-3beta gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians.
abstract: Mutations in genes encoding hepatocyte nuclear factor (HNF) are responsible for three of the five subtypes of maturity-onset diabetes of the young (MODY). This observation and molecular studies indicate that the HNF network is required for normal function of pancreatic beta-cells. This suggests that transcription factors involved in this complex network are candidates for genetic defects in MODY. Because the HNF-3beta gene is implicated in this network, we screened it for mutations in 21 probands of French ancestry with clinical diagnosis of MODY and early-onset type 2 diabetes. All of the five known MODY genes, HNF-4alpha, glucokinase, HNF-1alpha, HNF-1beta, and IPF1, were previously excluded as being the cause of diabetes in these families. By direct sequencing, we identified two transitions, an A-to-G at position -213 and a C-to-T at position -63 in the promoter and exon 1, respectively, of the HNF-3beta gene. A G-to-C transversion at position +32 in the intron 1 and three transitions, C-to-T at position 291, A-to-G at position 837, and G-to-A at position 1188 in the exon 3, resulting in noncoding mutations Ala97Ala, Gly279Gly, and Gln396Gln, respectively, were also identified. The allele frequencies were not significantly different between a control group and MODY probands. Familial segregation studies and linkage analysis showed that genetic variation in the HNF-3beta gene is unlikely to be the cause of early-onset type 2 diabetes in these Caucasian families.
authors.affiliation: Unité Propre de Recherche de l'Enseignement Supérieur Associée au Centre National de la Recherche Scientifique (CNRS UPRES-A) 8090, Institut de Biologie de Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Abderrahmani
authors.forename: J C
authors.initials: JC
authors.lastname: Chèvre
authors.forename: S
authors.initials: S
authors.lastname: Otabe
authors.forename: M
authors.initials: M
authors.lastname: Chikri
authors.forename: E H
authors.initials: EH
authors.lastname: Hani
authors.forename: M
authors.initials: M
authors.lastname: Vaxillaire
authors.forename: Y
authors.initials: Y
authors.lastname: Hinokio
authors.forename: Y
authors.initials: Y
authors.lastname: Horikawa
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
authors.forename: P
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000328:Adult; D017668:Age of Onset; D001483:Base Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005602:France; D008040:Genetic Linkage; D014644:Genetic Variation / Q000235:genetics*; D051542:Hepatocyte Nuclear Factor 3-beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D014157:Transcription Factors; D044465:White People / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C496502:FOXA2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta