A naturally occurring variant of endothelial lipase associated with elevated HDL exhibits impaired synthesis

作者：Brown Robert J; Edmondson Andrew C; Griffon Nathalie; Hill Theophelus B; Fuki Ilia V; Badellino Karen O; Li Mingyao; Wolfe Megan L; Reilly Muredach P; Rader Daniel J^*

来源：The Journal of Lipid Research, 2009, 50(9): 1910-1916.

DOI：10.1194/jlr.P900020-JLR200

• high density lipoprotein
• human subjects
• single nucleotide polymorphism
• protein translation
• lysosomal degradation
• proteosomal degradation

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.-Brown, R. J., A. C. Edmondson, N. Griffon, T. B. Hill, I. V. Fuki, K. O. Badellino, M. Li, M. L. Wolfe, M. P. Reilly, and D. J. Rader. A naturally occurring variant of endothelial lipase associated with elevated HDL exhibits impaired synthesis. J. Lipid Res. 2009. 50: 1910-1916.

• 出版日期2009-9