Genetic variation in the hepatocyte nuclear factor-3beta gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians.

Détails

ID Serval
serval:BIB_446537E52A13
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Genetic variation in the hepatocyte nuclear factor-3beta gene (HNF3B) does not contribute to maturity-onset diabetes of the young in French Caucasians.
Périodique
Diabetes
Auteur(s)
Abderrahmani A., Chèvre J.C., Otabe S., Chikri M., Hani E.H., Vaxillaire M., Hinokio Y., Horikawa Y., Bell G.I., Froguel P.
ISSN
0012-1797
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
49
Numéro
2
Pages
306-308
Langue
anglais
Résumé
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.
Mots-clé
Adult, Age of Onset, Base Sequence, DNA-Binding Proteins, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, France, Genetic Variation, Hepatocyte Nuclear Factor 3-beta, Humans, Linkage (Genetics), Male, Middle Aged, Nuclear Proteins, Transcription Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:16
Dernière modification de la notice
20/08/2019 13:48
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