A phenocopy of type III dysbetalipoproteinemia occurring in a candidate family for a putative apo E receptor defect.
On theoretical grounds, an apo E receptor defect should be manifested by the accumulation of lipoprotein remnants that are normally cleared by this receptor and cannot be processed by the normal apo B, E receptor (LDL-receptor). Furthermore, the defect should not be selective for a specific apo E phenotype since none of the isoforms would be cleared preferentially. Our search for such an occurrence led us to the discovery, in five members of a family of ten, of a unique dyslipoproteinemia mimicking type III. As in type III, plasma levels of cholesterol, triglycerides, VLDL-cholesterol, VLDL-triglycerides and apo E, as well as the VLDL-C/TG ratio, were high. LDL-cholesterol and HDL-cholesterol tended to be low. The clearance of plasma triglycerides after a fat load was impaired. Tubero-eruptive xanthomas, arcus corneae and manifestations of atherosclerosis were present in some individuals. In contrast to type III, the dyslipoproteinemia occurred in subjects bearing three different apo E phenotypes: E4/2, E4/3 and E3/2. VLDL-apo B levels were markedly increased, the VLDL-C/VLDL-B ratio was low and a double pre-beta band was present on lipoprotein electrophoresis. In spite of high apo E and borderline high apo CIII plasma levels, levels of the lipoprotein particles LpCIII:B and LpE:B, which characterize type III, were not raised. Rapid weight loss or treatment with a fibrate was observed to normalize the lipoprotein profile. It is surmised that the apo E-rich lipoprotein particles accumulating in this type III phenocopy with "hyperapoprebetalipoproteinemia" could be those that are normally cleared by an apo E receptor.
Davignon
J
J
Clinical Research Institute of Montreal, Department of Medicine, University of Montreal, Canada.
Dallongeville
J
J
Roederer
G
G
Roy
M
M
Fruchart
J C
JC
Kessling
A M
AM
Bouthillier
D
D
Lussier-Cacan
S
S
D000328:Adult; D001057:Apolipoproteins E / Q000097:blood; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008074:Lipoproteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011956:Receptors, Cell Surface; D014280:Triglycerides; D002784:Cholesterol