文章基本信息

标题：A naturally occurring variant of endothelial lipase associated with elevated HDL exhibits impaired synthesis
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作者：Robert J. Brown ; Andrew C. Edmondson ; Nathalie Griffon 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2009
卷号：50
期号：9
页码：1910-1916
DOI：10.1194/jlr.P900020-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Human endothelial lipase (EL) is a member of a family of lipases and phospholipases that are involved in the metabolism of plasma lipoproteins. EL displays a preference to hydrolyze lipids in HDL. We report here that a naturally occurring low frequency coding variant in the EL gene ( LIPG ), glycine-26 to serine (G26S), is significantly more common in African-American individuals with elevated HDL cholesterol (HDL-C) levels. To test the hypothesis that this variant results in reduced EL function, we extensively characterized and compared the catalytic and noncatalytic functions of the G26S variant and wild-type (WT) EL. While the catalytic-specific activity of G26S EL is similar to WT EL, its secretion is markedly reduced. Consistent with this observation, we found that carriers of the G26S variant had significantly reduced plasma levels of EL protein. Thus, this N-terminal variant results in reduced secretion of EL protein, plausibly leading to increased HDL-C levels.
关键词：high density lipoprotein ; human subjects ; single nucleotide polymorphism ; protein translation ; lysosomal degradation ; proteosomal degradation