Source:http://linkedlifedata.com/resource/pubmed/id/16731855
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2006-5-29
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| pubmed:abstractText |
Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total cholesterol compared with matched control subjects. Furthermore, the mutation disrupted the binding of an unidentified sequence-specific DNA binding complex present in human islet extracts. Also, two novel linked polymorphisms in the P2 promoter at positions -1107g/t and -858c/t were identified. These variants were not significantly associated with type 2 diabetes or any pre-diabetic traits. In conclusion, a rare, novel mutation that disrupts a protein binding site in the pancreatic HNF4A promoter associates with late-onset diabetes.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
|
| pubmed:issn |
0012-1797
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| pubmed:author |
pubmed-author:AlbrechtsenAndersA,
pubmed-author:BoesgaardTrine WTW,
pubmed-author:BojSylvia FSF,
pubmed-author:Borch-JohnsenKnutK,
pubmed-author:DammPeterP,
pubmed-author:EkJakobJ,
pubmed-author:FerrerJorgeJ,
pubmed-author:HansenSara PSP,
pubmed-author:HansenTorbenT,
pubmed-author:JørgensenTorbenT,
pubmed-author:JohansenAndersA,
pubmed-author:LajerMariaM,
pubmed-author:LakeR IRI,
pubmed-author:LauenborgJeannetJ,
pubmed-author:NicotCarineC,
pubmed-author:ParrizasMarcelinaM,
pubmed-author:PedersenOlufO,
pubmed-author:PruhovaStepankaS,
pubmed-author:YderstraedeKnudK
|
| pubmed:issnType |
Print
|
| pubmed:volume |
55
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1869-73
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16731855-Adult,
pubmed-meshheading:16731855-Age Factors,
pubmed-meshheading:16731855-Aged,
pubmed-meshheading:16731855-Binding Sites,
pubmed-meshheading:16731855-Blood Glucose,
pubmed-meshheading:16731855-Body Mass Index,
pubmed-meshheading:16731855-Diabetes Mellitus, Type 2,
pubmed-meshheading:16731855-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:16731855-Female,
pubmed-meshheading:16731855-Genotype,
pubmed-meshheading:16731855-Haplotypes,
pubmed-meshheading:16731855-Hepatocyte Nuclear Factor 4,
pubmed-meshheading:16731855-Humans,
pubmed-meshheading:16731855-Male,
pubmed-meshheading:16731855-Middle Aged,
pubmed-meshheading:16731855-Mutation,
pubmed-meshheading:16731855-Pedigree,
pubmed-meshheading:16731855-Polymorphism, Single Nucleotide,
pubmed-meshheading:16731855-Promoter Regions, Genetic,
pubmed-meshheading:16731855-Protein Binding,
pubmed-meshheading:16731855-Sex Factors
|
| pubmed:year |
2006
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| pubmed:articleTitle |
A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes.
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| pubmed:affiliation |
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|