Pancreatic Islet Expression Studies and Polymorphic DNA Markers in the Genes Encoding Hepatocyte Nuclear Factor-3α, -3β, -3γ, -4γ, and -6

The genes encoding the functionally related hepatocyte nuclear factors HNF-1α and HNF-4α play a critical role in normal pancreatic β-cell function. Mutations in these liver-enriched transcription factors result in two forms of early-onset type 2 diabetes (maturity-onset diabetes of the young [MODY]), M0DY3 and M0DY1, which are characterized by impaired glucose-stimulated insulin secretion, early disease onset, and autosomal dominant inheritance. The transcriptional hierarchy of HNFs suggests that other proteins of the regulatory cascade might be responsible for other forms of MODY and/or late-onset type 2 diabetes. In this study, we show that HNF-3α, -3β, -3γ, -4γ, and -6 are expressed in pancreatic β-cells. We report the identification and characterization of simple tandem repeat DNA polymorphisms in the genes encoding HNF-3α, -3β, -3γ, -4γ, and -6 and the mapping of HNF-6 to chromosome bands 15q21.1–21.2 by fluorescence in situ hybridization. These markers will be useful to study the role of genetic variation in these genes in the pathogenesis of type 2 diabetes.