Original Paper

The Human HNF-3 Genes: Cloning, Partial Sequence and Mutation Screening in Patients with Impaired Glucose Homeostasis
M. Angeles Navas^a, Christian Vaisse^a,b, Stephanie Boger^a, Markus Heimesaat^a, Louis A. Kollee^c, Markus Stoffel<sup>a

a</sup>Laboratory of Metabolic Diseases, The Rockefeller University, New York, N.Y.,
^bDepartment of Endocrinology, University of California San Francisco, San Francisco, Calif., USA;
^cDepartment of Pediatrics, University of Nijmegen, Nijmegen, The Netherlands

Address of Corresponding Author

Hum Hered 2000;50:370-381 (DOI: 10.1159/000022943)

  Key Words

• Hepatocyte nuclear factor
• Diabetes mellitus
• Hypoglycemia
• Polymorphisms

  Abstract

Hepatocyte nuclear factors 3 (HNF-3, -3 and -3) belong to an evolutionarily conserved family of transcription factors that are critical for diverse biological processes such as development, differentiation and metabolism. Gene expression studies have shown that HNF3 proteins are critical regulators of the early-onset type 2 diabetes genes HNF-1, HNF-4 and IPF-1/PDX-1 (MODY3, 1 and 4, respectively) and of glucagon transcription and pancreatic -cell function. In this study, we investigated whether genetic variation in the genes encoding HNF-3, HNF-3 and HNF-3 predisposes humans to hyperglycemic or hypoglycemic syndromes. In addition, we report the cloning and partial nucleotide sequence of the human HNF-3, -3 and -3 genes. Mutation screening included 96 subjects with type 2 diabetes mellitus, as well as one family with persistent neonatal hypoglycemia. No functional mutations were detected in the coding sequences of the three HNF-3 genes. Our results suggest that mutations in HNF-3 genes are not a common cause of type 2 diabetes mellitus. The data provided will facilitate genetic studies in other populations and will advance our understanding of the role HNF-3 plays in the development of diabetes mellitus and other metabolic disorders of glucose homeostasis.

Copyright © 2000 S. Karger AG, Basel

  Author Contacts

Markus Stoffel, MD, PhD
Laboratory of Metabolic Diseases, The Rockefeller University
1230 York Avenue, Box 292
New York, NY 10021 (USA)
Tel. +1 212 327 8797, Fax +1 212 327 7997, E-Mail stoffel@rockvax.rockefeller.edu

  Article Information

Received: Received: October 30, 1999
Accepted: November 22, 1999
Number of Print Pages : 12
Number of Figures : 4, Number of Tables : 4, Number of References : 39