CLINICAL PERSPECTIVE

This Article Abstract Full Text (PDF) Data Supplement Correction (v118,pe82) All Versions of this Article: 116/10/1185    most recent CIRCULATIONAHA.107.704346v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cox, L. A. Articles by VandeBerg, J. L. Search for Related Content PubMed PubMed Citation Articles by Cox, L. A. Articles by VandeBerg, J. L. Pubmed/NCBI databases Substance via MeSH Related Collections Risk Factors Functional genomics Gene expression Gene regulation Genetics of cardiovascular disease

(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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This Article Abstract Full Text (PDF) Data Supplement Correction (v118,pe82) All Versions of this Article: 116/10/1185    most recent CIRCULATIONAHA.107.704346v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cox, L. A. Articles by VandeBerg, J. L. Search for Related Content PubMed PubMed Citation Articles by Cox, L. A. Articles by VandeBerg, J. L. Pubmed/NCBI databases Substance via MeSH Related Collections Risk Factors Functional genomics Gene expression Gene regulation Genetics of cardiovascular disease