Linked Life Data

9017511

Source:http://linkedlifedata.com/resource/pubmed/id/9017511

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-9-2
pubmed:abstractText
Apolipoprotein (apo) C-II plays a major role as a cofactor for lipoprotein lipase, the enzyme involved in the hydrolysis of triglyceride-rich particles. We identified in two relatives of a family (mother and son) massive hypertriglyceridemia with chylomicronemia. In these individuals apoC-II was not measurable in plasma by radial immunodiffusion. On isoelectric focusing of very low density apolipoproteins, trace amounts of apoC-II became obvious in the regular position. By sequencing, no abnormalities in the exons or neighboring intron sequences were detected. However, three alterations in the DNA sequence were found upstream from the transcription initiation site. Two variations could be explained by differences in previously published DNA sequences. The third variation (A-->G; position -86; Das et al. 1987. J. Biol. Chem. 262: 4787-4793) was present only in the homozygous form in the two hypertriglyceridemic probands. In 46 hypertriglyceridemic individuals outside the family, this mutation was not found. In electrophoretic mobility shift experiments with nuclear extracts from HepG2 cells, the 31 bp DNA fragment carrying the A-->G substitution resulted in a markedly diminished protein binding compared with the wildtype DNA fragment. In promoter reporter gene assays, the activity of the basal promoter was reduced in the case of the A-->G substitution and the deletion of the bases -91 to -58. The pedigree analysis and the experimental results are evidence that this is the first mutation in the apolipoprotein C-II gene where a single nucleotide substitution diminishes the binding of a transcription factor to a positive cis-acting clement in the promoter resulting in a depletion of apolipoprotein C-II in plasma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2599-607
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
A single nucleotide substitution in the promoter region of the apolipoprotein C-II gene identified in individuals with chylomicronemia.
pubmed:affiliation
Klinik II und Poliklinik für Innere Medizin, Universität zu Köln, Germany.
pubmed:publicationType
Journal Article