CDB25:0003142 APOE — LSR
Experimentally validated in Human, Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Effect of LSR polymorphism on blood lipid levels and age-specific epistatic interaction with the APOE common polymorphism.
Clinical genetics, 2018; PubMed, Homo sapiens APOE — Homo sapiens LSR
ABSTRACT: The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride-rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328, <18 years old) from the STANISLAS Family Study were used. Age-specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, ApoE and low-density lipoprotein levels (β: .114, P: .777 × 10-8 , β: .125, P: .639 × 10-3 , β: .059, P: .531 × 10-3 , respectively). This interaction was verified in an independent adult population (n = 1744). These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in CVD pathology.
Identification of a lipolysis-stimulated receptor that is distinct from the LDL receptor and the LDL receptor-related protein.
Biochemistry, 1994; PubMed, Homo sapiens APOE — Rattus norvegicus Lsr
ABSTRACT: This paper provides further characterization of a receptor that, in cells lacking the LDL receptor (FH fibroblasts), mediates lipoprotein binding, uptake, and degradation when incubated with oleate at concentrations not exceeding albumin binding capacity. This oleate-activated receptor is genetically distinct from the LDL receptor and is hereafter referred to as the lipolysis-stimulated receptor (LSR). Its apparent affinity was higher for triglyceride-rich lipoproteins (chylomicrons, VLDL) and for lipid emulsions supplemented with recombinant apoE, than for LDL which contains solely apoB. In contrast, VLDL isolated from a Type III hyperlipidemic patient (apoE2/2 phenotype) failed to bind to the LSR. Five lines of evidence indicated that the LSR is distinct from the LDL receptor-related protein (LRP): (1) the LRP ligand, alpha 2-macroglobulin-methylamine (alpha 2-MG*), did not bind to the oleate-induced LDL binding site; (2) oleate had no effect on the binding of alpha 2-MG* to LRP; (3) the LRP-associated protein, RAP, which inhibits LRP, had no effect on the LSR; (4) binding of lipoproteins to LSR was independent of Ca2+; and (5) LSR activity resolved as two proteins smaller than LRP (apparent molecular masses as determined by ligand blots: 115 and 85 kDa). That LSR provides a new candidate receptor contributing to the clearance of chylomicron remnants (CMR) is supported by the observation that LSR was inhibited by lactoferrin, a milk protein that delays CMR clearance when injected in vivo. Furthermore, in primary cultures of rat hepatocytes, oleate stimulated binding, uptake, and degradation of LDL with kinetic characteristics similar to that of LSR expressed in FH fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)