Article: article from journal or magazin.
Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1alpha (TCF1) promoter region in MODY patients.
Maturity onset diabetes of the young (MODY) is a heterogeneous subtype of type II diabetes mellitus. To date, five MODY genes have been identified. Mutations in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene are associated with MODY3. In the present work, we implemented the HNF-1alpha promoter region in the screening of MODY-suspect patients and identified seven variants not detected in control subjects. The family was available for the -119delG variant, and segregration between MODY and the variant is observed. Most of these variants are located in highly conserved regions and may alter HNF-1alpha expression through binding alteration of nuclear factors or other mechanisms. We demonstrate by functional studies that the transcriptional activity of the -283A>C and -218T>C variant promoters were 30% and 70% of the wild type activity, respectively. These data suggest that HNF-1alpha promoter variants could be diabetogenic mutations, and emphasize that the accurate HNF-1alpha expression is important for the maintenance of normal pancreatic beta cell function.
5' Untranslated Regions, Adult, Age of Onset, Amino Acid Sequence, Base Sequence, Cell Line, Child, Preschool, Consensus Sequence, DNA, DNA-Binding Proteins, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Genetic Variation, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Humans, Male, Nuclear Proteins, Nucleotides, Pedigree, Polymorphism, Single-Stranded Conformational, Promoter Regions, Genetic, Response Elements, Transcription Factors
Web of science
Last modification date