dc.contributor.author | Macfarlane, Wendy M. | en_GB |
dc.contributor.author | Frayling, Timothy M. | en_GB |
dc.contributor.author | Ellard, Sian | en_GB |
dc.contributor.author | Evans, Julie C. | en_GB |
dc.contributor.author | Allen, Lisa I. S. | en_GB |
dc.contributor.author | Bulman, Michael P. | en_GB |
dc.contributor.author | Ayres, Susan | en_GB |
dc.contributor.author | Shepherd, Maggie H. | en_GB |
dc.contributor.author | Clark, Penny | en_GB |
dc.contributor.author | Millward, Ann | en_GB |
dc.contributor.author | Demaine, Andrew | en_GB |
dc.contributor.author | Wilkin, Terence | en_GB |
dc.contributor.author | Docherty, Kevin | en_GB |
dc.contributor.author | Hattersley, Andrew T. | en_GB |
dc.date.accessioned | 2007-05-14T09:22:25Z | en_GB |
dc.date.accessioned | 2011-01-25T10:08:03Z | en_GB |
dc.date.accessioned | 2013-03-20T17:07:39Z | |
dc.date.issued | 1999-11-01 | en_GB |
dc.description.abstract | The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic beta cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) when heterozygous. We studied the role of IPF-1 in Caucasian diabetic and nondiabetic subjects from the United Kingdom. Three novel IPF-1 missense mutations (C18R, D76N, and R197H) were identified in patients with type 2 diabetes. Functional analyses of these mutations demonstrated decreased binding activity to the human insulin gene promoter and reduced activation of the insulin gene in response to hyperglycemia in the human beta-cell line Nes2y. These mutations are present in 1% of the population and predisposed the subject to type 2 diabetes with a relative risk of 3.0. They were not highly penetrant MODY mutations, as there were nondiabetic mutation carriers 25-53 years of age. We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation. | en_GB |
dc.identifier.citation | Journal of Clinical Investigation, 1999, 104(9):R33-R39 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10036/11783 | en_GB |
dc.language.iso | en_US | en_GB |
dc.publisher | American Society for Clinical Investigation | en_GB |
dc.rights | Copyright © 1999, American Society for Clinical Investigation | en_GB |
dc.title | Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 1999-11-01 | en_GB |
dc.date.available | 2007-05-14T09:22:25Z | en_GB |
dc.date.available | 2011-01-25T10:08:03Z | en_GB |
dc.date.available | 2013-03-20T17:07:39Z | |
dc.identifier.issn | 0021-9738 | en_GB |
dc.format.dig | YES | en_GB |
dc.identifier.journal | Journal of Clinical Investigation | en_GB |
dc.identifier.pmcid | 481047 | en_GB |
dc.identifier.pmid | 10545530 | en_GB |