This review describes the history of development of our understanding of type III HLP, discusses the several genetic variants of apoE that play roles in the genesis of type III HLP, and describes the remarkable responsiveness of this fascinating disorder to lifestyle modification, especially carbohydrate restriction and calorie restriction, and, when required, the addition of pharmacotherapy.
Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL) receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP) in humans.
We have used adenovirus-mediated gene transfer in apolipoprotein (apo)E(-/-) mice to elucidate the molecular etiology of a dominant form of type III hyperlipoproteinemia (HLP) caused by the R142C substitution in apoE4.
To describe a patient with tuberous xanthomas and high levels of cholesterol and triglycerides, who was found to have type III hyperlipoproteinemia (HLP) and a rare apolipoprotein E (apoE) mutation.
To clarify a detailed profile of serum lipids, lipoproteins and apolipoproteins (apo) in type III hyperlipoproteinemia (HLP) with apolipoprotein E (apo E) phenotype 2/2.
Reduced expression of the LDLR is believed to be a precipitating factor in the pathogenesis of type III hyperlipoproteinemia (HLP) in some humans homozygous for the apoE2 allele (APOE*2).
This study examined whether apoE2 Sendai (Arg(145) Pro) was functionally different from type III HLP-producing apoE variants by expressing apoE3, apoE2 (Arg(158) Cys), apoE1 (Arg(146) Glu), a dominant apoE variant, and apoE2 Sendai (Arg(145) Pro) in the baculovirus system.
The definitive identification of a kindred with an apoE variant, apoE-1Harrisburg, dominantly associated with dysbetalipoproteinemia and type III HLP provides a unique opportunity to gain important insights into the structure-function requirements of the E apolipoprotein as well as the mechanisms by which apoE modulates lipoprotein metabolism.
Mutations in the 136-150 region of the N-terminal domain of apoE, reduce its low density lipoprotein (LDL) receptor binding capacity and have been linked with lipoprotein disorders, such as type III hyperlipoproteinemia (HLP) in humans.
The frequency of LPL gene mutation rates in HLP patients (17.0%, 9 of 53) was significantly higher than that without HLP attack (4.9%, 4 of 81) (P<0.0001).
Recessive type III HLP is caused by apoE2 (Arg(158) Cys), a mutant with diminished low-density lipoprotein (LDL) receptor binding but halfnormal heparin binding.
We conclude that a modest increase in expression of the LDLR through message stabilization is sufficient to prevent precipitation of type III HLP in mice.
The prevalence of heterozygosity for one of the four LPL mutant alleles in nondiabetic, nonobese hypertriglyceridemic subjects was 16 of 95 type IV HLP (17%) and 4 of 26 type V HLP cases (15%).
The common variant apoE2 and more than half a dozen rare variants are defective in binding to the low-density lipoprotein (LDL) receptor, and all are causally associated with the lipid disorder type III hyperlipoproteinaemia (HLP).
The present study was designed to determine whether the overexpression of cholesteryl ester transfer protein (CETP), a plasma protein that transfers cholesteryl esters from the high density lipoproteins (HDL) to the very low density lipoproteins (VLDL) and whose activity is increased in hyperlipidemic states, plays a role in the development of hyperlipidemia and beta-VLDL accumulation in type III HLP.
Methylation of B1 repetitive elements was significantly increased in the HHcy group (0.5050 ± 0.0182) compared to the HLP (0.5158 ± 0.0163) and control (0.5589 ± 0.0236) groups. mRNA and protein expressions of LOX-1 increased (0.2877 ± 0.0341, 0.6090 ± 0.0547), whereas methylation expression decreased (0.5527 ± 0.0148) after 100 μM Hcy stimulation in ECs.
The frequency of the rare allele of APOC3 3238 G>C and APOA5 -1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05).
The frequency of the rare allele of APOC3 3238 G>C and APOA5 -1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05).