Sökning: (WFRF:(Hamsten Anders)) srt2:(2005-2009)
> (2006) >
Allele-specific MMP...
Abstract
Ämnesord
Stäng
- A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1 beta, the haplotype containing the 5A-allete was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.
Nyckelord
- matrix metalloproteinases
- polymorphism
- promoter
- transcription
- inflammation
- haplochip
- 5a/6a promoter polymorphism
- coronary-artery-disease
- myocardial-infarction
- matrix-metalloproteinase
- stromelysin promoter
- gene-transcription
- heart-disease
- atherosclerosis
- progression
- matrix-metalloproteinase-3
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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