A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus

The Journal of Clinical Investigation
E H HaniP Froguel

Abstract

Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by hyperglycemia resulting from defects in insulin secretion and action. Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. During the course of our search for susceptibility genes contributing to the more common late-onset NIDDM forms, we observed nominal evidence for linkage between NIDDM and markers in the region of the HNF-4alpha/MODY1 locus in a subset of French families with NIDDM diagnosed before 45 yr of age. Thus, we screened these families for mutations in the HNF-4alpha gene. We found a missense mutation, resulting in a valine-to-isoleucine substitution at codon 393 in a single family. This mutation cosegregated with diabetes and impaired insulin secretion, and was not present in 119 control subjects. Expression studies showed that this conservative substitution is associated with a marked reduction of transactivation activity, a result consistent with this mutation contributing to the insulin secr...Continue Reading

References

Jan 1, 1990·Diabetes Care·S S Fajans
Aug 1, 1995·Proceedings of the National Academy of Sciences of the United States of America·O BoussifJ P Behr
Mar 11, 1993·The New England Journal of Medicine·P FroguelP Passa
Jan 3, 1997·The Journal of Biological Chemistry·M Hadzopoulou-CladarasJ A Ladias
Oct 1, 1996·Molecular Endocrinology·K B HorwitzL Tung

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Citations

Mar 20, 2003·Current Diabetes Reports·David Q Shih, Markus Stoffel
Mar 30, 2005·Current Diabetes Reports·Karen L Mohlke, Michael Boehnke
Mar 26, 2008·Endocrine·Debra F Skafar, Changqing Zhao
Jan 27, 2004·Molecular Genetics and Metabolism·Allison M BagwellDonald W Bowden
Dec 12, 2001·Molecular and Cellular Endocrinology·V M Schwitzgebel
Jan 16, 1999·Current Opinion in Biotechnology·J Bell
May 14, 1999·Trends in Endocrinology and Metabolism : TEM·P Froguel, G Velho
Jun 27, 2002·Molecular Genetics and Metabolism·Simon M S MitchellTimothy M Frayling
Oct 3, 2002·Molecular Genetics and Metabolism·Simon M S Mitchell, Timothy M Frayling
Apr 15, 2008·Médecine sciences : M/S·Thomas CadoudalClaude Forest
Sep 29, 2001·The New England Journal of Medicine·S S FajansK S Polonsky
Aug 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Qingqing LiuHarvey F Lodish
May 9, 2006·Current Opinion in Lipidology·Jussi NaukkarinenLeena Peltonen
Apr 19, 2012·PLoS Genetics·Pranali P PathareMarc R Van Gilst
Feb 21, 2009·PloS One·Pelin AkanPanagiotis Deloukas
Sep 14, 2012·The Review of Diabetic Studies : RDS·Mariana MureaBarry I Freedman
Jun 26, 2015·International Journal of Molecular Sciences·Rui ZhangGuoxun Chen
Feb 26, 2009·Expert Opinion on Drug Metabolism & Toxicology·John Y L Chiang
Jul 18, 2015·Molecular and Cellular Endocrinology·Shivali R Patel, Debra F Skafar
Apr 24, 2012·Journal of Lipids·Roman MüllenbachFrank Lammert
Sep 2, 2006·Drug Metabolism and Pharmacokinetics·Hiromi Fukushima-UesakaJun-Ichi Sawada
Sep 14, 2001·Best Practice & Research. Clinical Endocrinology & Metabolism·K Owen, A T Hattersley
Feb 6, 2007·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Jim KaputAmelia Bartholomew
Feb 11, 2010·Journal of Diabetes Science and Technology·R David G Leslie, Robert M Cohen
May 5, 1999·Diabetic Medicine : a Journal of the British Diabetic Association·M T MaleckiA S Krolewski
May 30, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·C PramfalkP Parini
Oct 13, 2007·The EMBO Journal·Xiaoling QuYu-Chung Yang
Jun 19, 2008·Diabetes/metabolism Research and Reviews·Jianmin HuangDavid B Rhoads
Oct 26, 1999·Endocrine Reviews·V Giguère
Nov 30, 2006·Pharmacological Reviews·Gérard BenoitVincent Laudet

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