Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations 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.
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PMID:Studies 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. 1166 23

HNF1-alpha is a transcription factor present in beta-cells. Mutations in the HNF1-alpha gene cause maturity-onset diabetes of the young (MODY), but the exact mechanism is not known. Several studies have highlighted genes down-regulated in beta-cells lacking this gene, but it is not clear if these are directly regulated by HNF1-alpha. To better understand this, we used human and mouse genome data to examine 29 genes expressed in the beta-cell. Using an in silico approach (with software available at www.BindGene.org) we examined 2kb upstream of each gene for possible HNF1 binding sequences. In five genes we also examined 100kb upstream of each gene, but only the portions strongly conserved between humans and mice. We identified nine putative HNF1 binding sites upstream of seven genes (p<0.1 and good alignment between species or p<0.05). Six of these nine sites had some experimental corroboratory evidence and included the recently identified sites 6 and 45kb upstream of HNF4-alpha. Three novel sites were identified. These were 92bp upstream of SLC3A1, 52bp upstream of PCBD (DCOH), and 42202bp upstream of TCF2(HNF1-beta). In conclusion, our computer search identified some known HNF1 sites, and suggested three novel sites indicating these genes are very likely to be directly activated by HNF1. This should help in designing experiments to discover the mechanisms of beta-cell dysfunction due to HNF1 disruption.
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PMID:In silico searching of human and mouse genome data identifies known and unknown HNF1 binding sites upstream of beta-cell genes. 1261 86