Linked Life Data

11668623

Source:http://linkedlifedata.com/resource/pubmed/id/11668623

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pubmed-article:11668623pubmed:dateCreated2001-10-22lld:pubmed
pubmed-article:11668623pubmed:abstractTextMutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy, and 46 type 2 diabetic patients with an impaired beta-cell function by combined single-strand conformation polymorphism (SSCP) and heteroduplex analysis. Analysis of the promoter and nine exons including intron-exon boundaries of the HNF-1beta gene revealed one novel silent polymorphism and three previously reported intronic variants. The silent polymorphism (I91I) was found in one patient with late-onset type 2 diabetes. One of the intronic variant (IVS6+26T-->C) was examined further. Among 584 type 2 diabetic patients the allelic frequency was 13.1% (11.2-15.0%) compared to 11.6% (8.6-14.5%) in 229 glucose tolerant control subjects (NS). No difference in insulin secretion during an OGTT was seen between carriers of the different IVS6+26T-->C genotypes among the 229 middle-aged control subjects, nor among 302 glucose tolerant 60-year-old Danish Caucasians. Mutation analysis of the four exons comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects.lld:pubmed
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pubmed-article:11668623pubmed:copyrightInfoCopyright 2001 Wiley-Liss, Inc.lld:pubmed
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pubmed-article:11668623pubmed:articleTitleStudies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function.lld:pubmed
pubmed-article:11668623pubmed:affiliationSteno Diabetes Center and Hagedorn Research Institute, Gentofte, Copenhagen, Denmark.lld:pubmed
pubmed-article:11668623pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11668623pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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