Background: Loss of function variants of LIPG gene encoding endothelial lipase (EL) are associated with primary hyperalphalipoproteinemia (HALP), a lipid disorder characterized by elevated plasma levels of high density lipoprotein cholesterol (HDL-C).
Objective: Aim of the study was the phenotypic and genotypic characterization of a family with primary HALP.
Methods: HDL subclasses distribution was determined by polyacrylamide gradient gel electrophoresis. Serum content of preβ-HDL was assessed by (2D)-electrophoresis. Cholesterol efflux capacity (CEC) of serum mediated by ABCA1, ABCG1 or SR-BI was assessed using cells expressing these proteins. Cholesterol loading capacity (CLC) of serum was assayed using cultured human macrophages. Next generation sequencing was used for DNA analysis. Plasma EL mass was determined by ELISA.
Results: Three family members had elevated plasma HDL-C, apoA-I and total phospholipids, as well as a reduced content of preβ-HDL. These subjects were heterozygous carriers of a novel variant of LIPG gene [c.526 G>T, p.(Gly176Trp)] found to be deleterious in silico. Plasma EL mass in carriers was lower than in controls. CEC of sera mediated by ABCA1 and ABCG1 transporters was substantially reduced in the carriers. This effect was maintained after correction for serum HDL concentration. The sera of carriers were found to have a higher CLC in cultured human macrophages than control sera.
Conclusion: The novel p.(Gly176Trp) variant of endothelial lipase is associated with changes in HDL composition and subclass distribution as well as with functional changes affecting cholesterol efflux capacity of serum which suggest a defect in the early steps of revere cholesterol transport.
Keywords: Cholesterol efflux capacity; Cholesterol loading capacity; Endothelial Lipase; High density lipoprotein composition; High density lipoprotein subclasses; Missense variant; Primary hyperalphalipoproteinemia.
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