Identification of promoter variants in baboon endothelial lipase that regulate high-density lipoprotein cholesterol levels

Article

关键词: LINKAGE ANALYSIS;    GENETIC-LINKAGE;    MOLECULAR-BASIS;    FAMILIAL LECITHIN;    CANDIDATE GENES;    GRADIENT GEL;    HDL;    DEFICIENCY;    SERUM;    SUBFRACTIONS;   

DOI  :  10.1161/CIRCULATIONAHA.107.704346

来源: SCIE

【 摘 要 】

Background-High-density lipoprotein cholesterol (HDL) levels are a major risk factor for cardiovascular disease. Previously we identified a quantitative trait locus on baboon chromosome 18 that regulates HDL. From positional cloning studies and expression studies, we identified the endothelial lipase gene ( LIPG) as the primary candidate gene for the quantitative trait locus. The mechanism by which LIPG variation influences HDL levels has not been determined. Methods and Results-We identified 164 LIPG polymorphisms in a panel of sibling baboons discordant for HDL1 and genotyped putative regulatory polymorphisms in a population of 951 pedigreed baboons. With the use of quantitative trait nucleotide analysis we identified 3 polymorphisms in the LIPG promoter associated with variation in serum HDL1 levels. In addition, we demonstrated that these 3 polymorphisms affect LIPG promoter activity in vitro. In silico analysis was used to identify putative transcription factors that differentially bind the functional promoter polymorphisms. Conclusions-These results reveal LIPG variants that specifically contribute to HDL1 levels and demonstrate mechanisms by which these polymorphisms may regulate LIPG promoter activity. Results from the present study provide a mechanism, namely variation in LIPG promoter activity possibly caused by altered transcription factor binding, by which LIPG variation affects HDL levels.

【 授权许可】

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