Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant renal disease with incomplete penetrance, associated with specific protein-modifying mutations in the APOE gene.
Familial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all ε2 homozygotes develop FD indicating that additional factors play a role including insulin resistance (IR).
Renal biopsy revealed typical LPG lesions with whorled, mesh-like material in dilated glomerular capillary lumens that stained positive for Sudan Ⅲ and apoE. apoE gene analysis revealed a T-to-C point mutation at amino acid 173 that caused a substitution of a proline residue for a leucine residue, which has not been reported previously.
Most familial dysbetalipoproteinemia patients are homozygous for apolipoprotein ε2, which is associated with decreased binding of apolipoprotein E to the LDL receptor.
We evaluated whether and to what extent the APOE genotype modifies the relation between adiposity and lipids in patients with manifest arterial disease and we looked at possible determinants of DBL in ɛ2 homo- and heterozygote patients.
The identification of a patient with a rare form of severe dysbetalipoproteinemia allowed the study of the consequences of total absence of apolipoprotein E (apoE).
On the other hand, the administration of fibrate with the intensive control of triglyceride and apolipoprotein E particularly from the early phase will ameliorate LPG and prevent renal dysfunction.
Rarely, mutations in apolipoprotein E are associated with lipoprotein glomerulopathy, a condition characterized by progressive proteinuria and renal failure with varying degrees of plasma remnant accumulation.
Lipoprotein glomerulopathy is an inherited renal disease characterized by unique lipoprotein thrombi in the glomerulus and is associated with the APOE mutation.
The recognition that structural destabilization may underlie the association between apoE mutations and LPG can be key for development of new innovative treatments for this rare disease.