Genetics
Novel CETP promoter variants found in hyperalphalipoproteinemia patients sharply cut gene transcriptional activity (Clin Chim Acta 2013)
Original title: Functional characterization of novel variants in the CETP promoter and the LIPC gene in subjects with hyperalphalipoproteinemia
This study functionally characterized three novel variants in the CETP promoter and two novel variants in the LIPC gene, previously identified in Thai subjects with hyperalphalipoproteinemia (HALP, high HDL-cholesterol), using site-directed mutagenesis and expression assays in HepG2 cells. For the CETP promoter variants, luciferase reporter assays showed markedly reduced transcriptional activity for -49G>T, -70C>T, and -372C>T, at 5%, 8%, and 30% of wild-type activity respectively (P less than 0.001). For the LIPC missense variants, hepatic lipase activity in cell lysates was 41% (c.421A>G, p.G141S) and 46% (c.517G>A, p.V173M) of wild-type activity (P less than 0.05). The authors conclude these newly identified CETP promoter and LIPC variants may contribute to HALP and could have diagnostic application in genetic evaluation of subjects with high HDL-cholesterol.
Original abstract
Background: Variants in the CETP and the LIPC genes, encoding cholesteryl ester transfer protein and hepatic lipase, respectively, are associated with high levels of HDL-cholesterol or hyperalphalipoproteinemia (HALP). Recently, we have identified three novel variants in the CETP promoter and two novel variants in LIPC in Thai subjects with HALP. In this study, we investigated the functions of these 5 variants in vitro.
Methods: For CETP promoter variants, we used site-directed mutagenesis, transient expression in HepG2 cells and luciferase reporter assay. For LIPC variants, cDNA was cloned and mutagenesis for missense variants was performed before expression in HepG2 cells.
Results: The transcriptional activities of -49G>T,-70C>T, and -372C>T CETP promoter variants were markedly reduced (5%, 8% and 30%, respectively, compared to that of the wild-type, P<0.001). For LIPC variants, hepatic lipase activities in the lysates of cells transfected with c.421A>G (p.G141S) and c.517G>A (p.V173M) variants were 41% and 46%, respectively, compared to that of the wild-type (P<0.05).
Conclusions: The recently-identified variants in the CETP promoter and in the LIPC gene may contribute to HALP. Our result may have a diagnostic application in the genetic evaluation of subjects with high HDL-cholesterol levels.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.