Apolipoprotein E ε 4 allele and nephrotic glomerular diseases in children

Abstract

Hyperlipidemia is a well-recognized complication of the nephrotic syndrome and is a factor contributing to the progression of the initial glomerular injury and the development of glomerulosclerosis. Apolipoprotein E (apoE) is a plasma protein and apoE epsilon 4 allele is associated with higher plasma cholesterol levels. With this in mind, we studied apoE phenotypes and alleles in children with nephrotic glomerular diseases (NGD, n=29), including idiopathic nephrotic syndrome (n=16), membranoproliferative glomerulonephritis (n=7), and focal segmental glomerulosclerosis (FSGS, n=6). Children with NGD had a higher epsilon 4 allele frequency (20.7%) than controls (10.8%), and those with FSGS had both higher apoE4/3 (66.7%) and epsilon 4 allele (33.3%) frequencies than controls (20.4% and 10.8%, respectively). In IgA nephropathy (n=30, disease controls), no significant association with specific apoE was found. Further studies are needed to clarify the significance of the observed high frequencies of apoE epsilon 4 allele in children with NGD and apoE4/3 phenotype distribution in FSGS.

Dyslipidemia and nephrotic syndrome: Recent advances

“…48 Therefore several studies investigated an association between the apo E polymorphism and NS in humans, and had contrasting findings. Smaller studies found an increase in the ⑀4 allele in childhood NS, 49 which was not confirmed by 2 larger studies. 50,51 A recent study found a tendency toward a higher frequency of ⑀4 allele in 190 nephrotic children, which became significant in those who had frequent disease relapses.…”

Serum Glomerular Permeability Activity in Patients with Podocin Mutations (NPHS2) and Steroid-ResistantNephrotic Syndrome

“…Serum levels of apo E were increased in nephrotic patients compared with normal controls, whereas apo E levels very low in urine. The genotype of apo E was in all cases E3/E3 encoding apo E 3 , the most frequent genotype (13).…”

A Form of Apolipoprotein A-I Is Found Specifically in Relapses of Focal Segmental Glomerulosclerosis Following Transplantation

“…It has been demonstrated that components of HDL inhibit glomerular albumin permeability induced by serum from patients with FSGS (25). Genetic variants of HDL components have been associated to idiopathic FSGS, such as ApoE (26) or paraoxonase (27), and specially the apolipoprotein L1 (28). This would result in altered HDL particles, which have been implicated in the pathogenesis of FSGS (29).…”