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Circulation. 2007;116:1185-1195
Published online before print August 20, 2007, doi: 10.1161/CIRCULATIONAHA.107.704346
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(Circulation. 2007;116:1185-1195.)
© 2007 American Heart Association, Inc.


Molecular Cardiology

CLINICAL PERSPECTIVE

High-density lipoprotein cholesterol (HDL) levels are a major risk factor for cardiovascular disease. In light of the recent cancellation of Torcetrapib clinical trials, it has become clear that new approaches to raise HDL must be developed. Studies in humans and mice indicate that endothelial lipase plays a major role in regulation of HDL levels by catalyzing the hydrolysis of HDL phospholipids and facilitating clearance of HDL from the circulation. The central question is whether genetic variation in the endothelial lipase gene (LIPG) influences variation in HDL. Association studies in humans and functional studies in mice support the hypothesis that genetic variation in LIPG significantly influences HDL. However, few if any LIPG polymorphisms have been rigorously demonstrated to affect endothelial lipase activity and function. Furthermore, the mechanism(s) by which LIPG variation influences HDL levels has not been determined. Results from our study demonstrate that variation of specific nucleotides in the LIPG promoter regulates LIPG expression and influences variation in HDL (specifically large HDL particles). On the basis of previous studies that compared functional variants in baboon and human genes, it is unlikely that the same polymorphisms in human LIPG gene promoter regulate HDL. However, it is likely that the same mechanism (ie, LIPG promoter variation regulation of LIPG expression) will be found to regulate human LIPG expression and influence HDL levels. Therefore, our findings suggest that HDL levels may be modified therapeutically via modulation of LIPG gene expression. Future studies will focus on identification of human LIPG functional variants that could serve as therapeutic targets to increase HDL levels.


*    Footnotes
 
The online-only Data Supplement, which contains tables, is available with this article at http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.107.704346/DC1.




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D. L. Rainwater, L. A. Cox, J. Rogers, J. L. VandeBerg, and M. C. Mahaney
Localization of multiple pleiotropic genes for lipoprotein metabolism in baboons
J. Lipid Res., July 1, 2009; 50(7): 1420 - 1428.
[Abstract] [Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow Correction (v118,pe82)
Right arrow All Versions of this Article:
116/10/1185    most recent
CIRCULATIONAHA.107.704346v1
Right arrow Alert me when this article is cited
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Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cox, L. A.
Right arrow Articles by VandeBerg, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cox, L. A.
Right arrow Articles by VandeBerg, J. L.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Related Collections
Right arrow Risk Factors
Right arrow Functional genomics
Right arrow Gene expression
Right arrow Gene regulation
Right arrow Genetics of cardiovascular disease