Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3)

Kazuya Yamagata, Naohisa Oda, Pamela J. Kaisaki, Stephan Menzel, Hiroto Furuta, Martine Vaxillaire, Lorraine Southam, Roger D. Cox, G. Mark Lathrop, V. Vicky Boriraj, Xiangna Chen, Nancy J. Cox, Yukie Oda, Hideki Yano, Michelle M. Le Beau, Shirou Yamada, Hidekazu Nishigori, Jun Takeda, Stefan S. Fajans, Andrew T. HattersleyNaoko Iwasaki, Torben Hansen, Oluf Pedersen, Kenneth S. Polonsky, Robert C. Turner, Gilberto Velho, Jean Claude Chèvre, Philippe Froguel, Graeme I. Bell

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1016 Citations (Scopus)


THE disease non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is characterized by abnormally high blood glucose resulting from a relative deficiency of insulin. It affects about 2% of the world's population and treatment of diabetes and its complications are an increasing health-care burden. Genetic factors are important in the aetiology of NIDDM, and linkage studies are starting to localize some of the genes that influence the development of this disorder. Maturity-onset diabetes of the young (MODY), a single-gene disorder responsible for 2-5% of NIDDM, is characterized by autosomal dominant inheritance and an age of onset of 25 years or younger. MODY genes have been localized to chromosomes 7, 12 and 20 (refs 5, 7, 8) and clinical studies indicate that mutations in these genes are associated with abnormal patterns of glucose-stimulated insulin secretion. The gene on chromosome 7 (MODY2) encodes the glycolytic enzyme glucokinase which plays a key role in generating the metabolic signal for insulin secretion and in integrating hepatic glucose uptake. Here we show that subjects with the MODY3-form of NIDDM have mutations in the gene encoding hepatocyte nuclear factor-1α (HNF-1α, which is encoded by the gene TCF1). HNF-1α is a transcription factor that helps in the tissue-specific regulation of the expression of several liver genes and also functions as a weak transactivator of the rat insulin-I gene.

Original languageEnglish
Pages (from-to)455-458
Number of pages4
Issue number6608
Publication statusPublished - 1996 Dec 5
Externally publishedYes

ASJC Scopus subject areas

  • General


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