Background. Lipid abnormalities are frequently found in end-stage renal dis
ease (ESRD), and abnormal lipid metabolism may contribute to the progressio
n of renal disease. Previous investigators have reported that apolipoprotei
n E (apoE) has an important role in lipoprotein metabolism and that the pro
cess of lipoprotein catabolism varies according to the apoE phenotype. In a
ddition, the relative frequency of the apoE alleles is different among the
races. In this study, we investigated the allele frequency of apoE phenotyp
es and evaluated the impact of apoE polymorphism on lipid profile in Japane
se patients with renal disease.
Methods. ApoE phenotypes were determined using isoelectric focusing and Wes
tern blotting in 592 Japanese patients with renal disease [86 out of 107 pa
tients with glomerulonephritis had proteinuria of not less than 0.25 g per
24 hr and 485 with ESRD; 448 were on hemodialysis (HD), and 37 were on cont
inuous ambulatory peritoneal dialysis (CAPP)I. The allele frequency and apo
E phenotype distribution were estimated by the gene-counting method. Serum
lipid parameters related to lipid metabolism were measured after at least a
12-hour fast.
Results. The allele frequency of the three major apoE phenotypes (apoE2, ap
oE3, and apoE4) in 107 glomerulonephritis patients (epsilon 2; 0.037, epsil
on 3; 0.860, epsilon 4; 0.103) was almost identical to that in the normal c
ontrol population (epsilon 2; 0.036, epsilon 3; 0.848, epsilon 4; 0.115). H
owever, 86 glomerulonephritis patients with proteinuria had higher allele f
requency of apoE2 (epsilon 2; 0.052, P < 0.01) and apoE4 (epsilon 4; 0.140,
P < 0.001) and lower allele frequency of apoE3 (epsilon 3; 0.808, P < 0.00
1) than the controls. Furthermore, ESRD patients had higher allele frequenc
y of apoE2 (epsilon 2; 0.058, P < 0.01) and lower allele frequency of apoE4
(epsilon 4; 0.091, P < 0.05) than the controls. Higher prevalence of nephr
otic syndrome was found in proteinuric glomerulonephritis patients with apo
E2. The impact of apoE polymorphism on serum lipid profile in patients with
glomerulonephritis, HD, and CAPD was different from that generally expecte
d.
Conclusions. The higher frequency of apoE2 in ESRD patients suggests that a
poE2 is a possible genetic predisposition to ESRD in a Japanese population.
The impact of apoE2 and apoE4 on lipid profile in patients with renal dise
ase was unique and different from that in the normal population.